Phase Separation in Cell Division.

Cell division requires the assembly and organization of a microtubule spindle for the proper separation of chromosomes in mitosis and meiosis. Phase separation is an emerging paradigm for understanding spatial and temporal regulation of a variety of cellular processes, including cell division. Phase-separated condensates have been recently discovered at many structures during cell division as a possible mechanism for properly localizing, organizing, and activating proteins involved in cell division. Here, we review how these condensates play roles in regulating microtubule density and organization and spindle assembly and function and in activating some of the key players in cell division. We conclude with perspectives on areas of future research for this exciting and rapidly advancing field.

Lack of p38 activation in T cells increases IL-35 and protects against obesity by promoting thermogenesis.

Obesity is characterized by low-grade inflammation, energy imbalance and impaired thermogenesis. The role of regulatory T cells (Treg) in inflammation-mediated maladaptive thermogenesis is not well established. Here, we find that the p38 pathway is a key regulator of T cell-mediated adipose tissue (AT) inflammation and browning. Mice with T cells specifically lacking the p38 activators MKK3/6 are protected against diet-induced obesity, leading to an improved metabolic profile, increased browning, and enhanced thermogenesis. We identify IL-35 as a driver of adipocyte thermogenic program through the ATF2/UCP1/FGF21 pathway. IL-35 limits CD8+ T cell infiltration and inflammation in AT. Interestingly, we find that IL-35 levels are reduced in visceral fat from obese patients. Mechanistically, we demonstrate that p38 controls the expression of IL-35 in human and mouse Treg cells through mTOR pathway activation. Our findings highlight p38 signaling as a molecular orchestrator of AT T cell accumulation and function.

The STARD9/Kif16a kinesin associates with mitotic microtubules and regulates spindle pole assembly.

During cell division, cells form the microtubule-based mitotic spindle, a highly specialized and dynamic structure that mediates proper chromosome transmission to daughter cells. Cancer cells can show perturbed mitotic spindles and an approach in cancer treatment has been to trigger cell killing by targeting microtubule dynamics or spindle assembly. To identify and characterize proteins necessary for spindle assembly, and potential antimitotic targets, we performed a proteomic and genetic analysis of 592 mitotic microtubule copurifying proteins (MMCPs). Screening for regulators that affect both mitosis and apoptosis, we report the identification and characterization of STARD9, a kinesin-3 family member, which localizes to centrosomes and stabilizes the pericentriolar material (PCM). STARD9-depleted cells have fragmented PCM, form multipolar spindles, activate the spindle assembly checkpoint (SAC), arrest in mitosis, and undergo apoptosis. Interestingly, STARD9-depletion synergizes with the chemotherapeutic agent taxol to increase mitotic death, demonstrating that STARD9 is a mitotic kinesin and a potential antimitotic target.

p38γ is essential for cell cycle progression and liver tumorigenesis.

The cell cycle is a tightly regulated process that is controlled by the conserved cyclin-dependent kinase (CDK)-cyclin protein complex1. However, control of the G0-to-G1 transition is not completely understood. Here we demonstrate that p38 MAPK gamma (p38γ) acts as a CDK-like kinase and thus cooperates with CDKs, regulating entry into the cell cycle. p38γ shares high sequence homology, inhibition sensitivity and substrate specificity with CDK family members. In mouse hepatocytes, p38γ induces proliferation after partial hepatectomy by promoting the phosphorylation of retinoblastoma tumour suppressor protein at known CDK target residues. Lack of p38γ or treatment with the p38γ inhibitor pirfenidone protects against the chemically induced formation of liver tumours. Furthermore, biopsies of human hepatocellular carcinoma show high expression of p38γ, suggesting that p38γ could be a therapeutic target in the treatment of this disease.

The DNA methyltransferase inhibitor decitabine blunts the response to a high-animal fat and protein diet in mice.

Increasing evidence hints that DNA hypermethylation may mediate the pathogenic response to cardiovascular risk factors. Here, we tested a corollary of that hypothesis, that is, that the DNA methyltransferase inhibitor decitabine (Dec) ameliorates the metabolic profile of mice fed a moderately high-animal fat and protein diet (HAFPD), a proxy of cardiovascular risk-associated Western-type diet. HAFPD-fed mice were exposed to Dec or vehicle for eight weeks (8W set, 4-32/group). To assess any memory of past exposure to Dec, we surveyed a second mice set treated as 8W but HAFPD-fed for further eight weeks without any Dec (16W set, 4-20/group). In 8W, Dec markedly reduced HAFPD-induced body weight gain in females, but marginally in males. Characterization of females revealed that Dec augmented skeletal muscle lipid content, while decreasing liver fat content and increasing plasma nonesterified fatty acids, adipose insulin resistance, and-although marginally-whole blood acylcarnitines, compared to HAFPD alone. Skeletal muscle mitochondrial DNA copy number was higher in 8W mice exposed to HAFPD and Dec, or in 16W mice fed HAFPD only, relative to 8W mice fed HAFPD only, but Dec induced a transcriptional profile indicative of ameliorated mitochondrial function. Memory of past Dec exposure was tissue-specific and sensitive to both duration of exposure to HAFPD and age. In conclusion, Dec redirected HAFPD-induced lipid accumulation toward the skeletal muscle, likely due to augmented mitochondrial functionality and increased lipid demand. As caveat, Dec induced adipose insulin resistance. Our findings may help identifying strategies for prevention and treatment of lipid dysmetabolism.

Myeloid p38 activation maintains macrophage-liver crosstalk and BAT thermogenesis through IL-12-FGF21 axis.

Obesity features excessive fat accumulation in several body tissues and induces a state of chronic low-grade inflammation that contributes to the development of diabetes, steatosis, and insulin resistance. Recent research has shown that this chronic inflammation is crucially dependent on p38 pathway activity in macrophages, suggesting p38 inhibition as a possible treatment for obesity comorbidities. Nevertheless, we report here that lack of p38 activation in myeloid cells worsens high-fat diet-induced obesity, diabetes, and steatosis. Deficient p38 activation increases macrophage IL-12 production, leading to inhibition of hepatic FGF21 and reduction of thermogenesis in the brown fat. The implication of FGF21 in the phenotype was confirmed by its specific deletion in hepatocytes. We also found that IL-12 correlates with liver damage in human biopsies, indicating the translational potential of our results. Our findings suggest that myeloid p38 has a dual role in inflammation and that drugs targeting IL-12 might improve the homeostatic regulation of energy balance in response to metabolic stress.

Insights from different reproductive gene knockdowns via RNA interference in the lady beetle Eriopis connexa: Establishing a new model for molecular studies on natural enemies.

Insect pest control can be achieved by the application of RNA interference (RNAi), a key molecular tool in functional genomics. Whereas most RNAi research has focused on insect pests, few studies have been performed on natural enemies. Validating the efficacy of RNAi in natural enemies is crucial for assessing its safety and enabling molecular research on these organisms. Here, we assessed the efficacy of RNAi in the ladybird beetle Eriopis connexa Germar (Coleoptera: Coccinellidae), focusing on genes related to reproduction, such as vitellogenin (Vg) and its receptor (VgR). In the transcriptome of E. connexa, we found one VgR (EcVgR) and two Vg genes (EcVg1 and EcVg2). These genes have been validated by in silico analyses of functional domains and evolutionary relationships. Five-day-old females were injected with 500 ng/µL of a specific double-stranded RNA (dsRNA) (dsEcVg1, dsEcVg2, or dsEcVgR) for RNAi tests, while nonspecific dsRNA (dsGFP or dsAgCE8.1) was used as a control. Interestingly, dsEcVg2 was able to knockdown both Vg genes, while dsEcVg1 could silence only EcVg1. Additionally, the viability of the eggs was significantly reduced when both Vg genes were knocked down at the same time (after treatment with dsEcVg2 or "dsEcVg1+dsEcVg2"). Ultimately, malformed, nonviable eggs were produced when EcVgR was silenced. Interestingly, no dsRNA treatment had an impact on the quantity of eggs laid. Therefore, the feasibility of RNAi in E. connexa has been confirmed, suggesting that this coccinellid is an excellent Neotropical model for molecular research on natural enemies and for studying RNAi nontarget effects.

Long-term suitability of an alternative host for rearing the sugarcane stalk borer parasitoid Tetrastichus howardi.

The continuous utilisation of an alternative host may influence parasitoid performance across successive generations due to conditioning in natal hosts. Tetrastichus howardi (Olliff) has successfully been reared using Tenebrio molitor L. pupae as a feasible alternative host. However, the extended rearing of T. howardi on this alternative host may impact the biological features of the parasitoids. Parasitoids were reared using T. molitor pupae for 30 consecutive generations. Quality criteria were assessed during the generations F5, F15, and F30, offering pupae of the target pest, Diatraea saccharalis (Fabr.), and compared with the F0 generation (parasitoids reared in D. saccharalis pupae). Criteria included assessments of parasitism performance, host selection, and wing form variation in the parasitoid wasps. Additionally, we examined the fecundity of T. howardi females that emerged from both hosts, considering their age, egg loading before and after one oviposition, as well as parasitism of sugarcane stalk borer pupae. Rearing T. howardi using pupae of T. molitor did not affect its biological traits or preference for the target pest for 30 generations. After parasitism, the parasitoid left the host pupa inside the stalk, and one oviposition was enough to kill D. saccharalis pupae and obtain viable parasitoid progeny. Female sexual maturation and egg loading occurred 72 and 96 h after parasitoid emergence. Egg-loading recovery after parasitism did not happen within 24 h. T. howardi can be reared for up to 30 generations using alternative hosts without compromising its parasitism performance or egg loading.

Design of a multiple criteria decision analysis framework for prioritizing high-impact health technologies in a regional health service.

OBJECTIVES: This study aims to develop a framework for establishing priorities in the regional health service of Murcia, Spain, to facilitate the creation of a comprehensive multiple criteria decision analysis (MCDA) framework. This framework will aid in decision-making processes related to the assessment, reimbursement, and utilization of high-impact health technologies. METHOD: Based on the results of a review of existing frameworks for MCDA of health technologies, a set of criteria was proposed to be used in the context of evaluating high-impact health technologies. Key stakeholders within regional healthcare services, including clinical leaders and management personnel, participated in a focus group (n = 11) to discuss the proposed criteria and select the final fifteen. To elicit the weights of the criteria, two surveys were administered, one to a small sample of healthcare professionals (n = 35) and another to a larger representative sample of the general population (n = 494). RESULTS: The responses obtained from health professionals in the weighting procedure exhibited greater consistency compared to those provided by the general public. The criteria more highly weighted were "Need for intervention" and "Intervention outcomes." The weights finally assigned to each item in the multicriteria framework were derived as the equal-weighted sum of the mean weights from the two samples. CONCLUSIONS: A multi-attribute function capable of generating a composite measure (multicriteria) to assess the value of high-impact health interventions has been developed. Furthermore, it is recommended to pilot this procedure in a specific decision context to evaluate the efficacy, feasibility, usefulness, and reliability of the proposed tool.

Synthesis of para-Acetylated Functionalized Ni(II)-POCOP Pincer Complexes and Their Cytotoxicity Evaluation Against Human Cancer Cell Lines.

A series of three Ni(II)-POCOP complexes para-functionalized with an acetoxyl fragment were synthesized. All complexes (2a-c) were fully characterized through standard analytical techniques. The molecular structure of complex 2b was unambiguously determined by single-crystal X-ray diffraction, revealing that the metal center is situated in a slightly distorted square-planar environment. Additionally, the acetoxy fragment at the para-position of the phenyl ring was found to be present. The in vitro cytotoxic activity of all complexes was assessed on six human cancer cell lines. Notably, complex 2b exhibited selective activity against K-562 (chronic myelogenous leukemia) and MCF-7 (mammary adenocarcinoma) with IC50 values of 7.32 ±â€¯0.60 µM and 14.36 ±â€¯0.02 µM, respectively. Furthermore, this compound showed negligible activity on the healthy cell line COS-7, highlighting the potential therapeutic application of 2b. The cytotoxic evaluations were further complemented with molecular docking calculations to explore the potential biological targets of complex 2b, revealing interactions with cluster differentiation protein 1a (CD1A, PDB: 1xz0) for K-562 and with the progesterone receptor for MCF-7.

Associations of fertility parameters with fatty acids and DNA methylation in Mexican women undergoing in vitro fertilization.

BACKGROUND: Fatty acids (FA) likely affect human fertility at multiple levels, as deviations from physiological FA profiles are obesogenic, and FA can modify DNA methylation (DNAm). Yet, the interplay of follicular fluid (FF) and serum FA with BMI and percentage body fat (PBF) in human fertility is not completely understood. Also, associations of DNAm with fertility are largely unexplored. METHODS: Reproductive parameters ranging from retrieved oocyte number to infant birth weight, were recorded in Mexican women undergoing in vitro fertilization (n = 88). Multiple regression analysis sought BMI-adjusted and age-adjusted associations. Receiver operating characteristic analysis tested for discrimination between outcomes. RESULTS: Associations of FF and serum FA were markedly distinct. While various FF FA (C16:1, C18:0, C20:2, C20:3, arachidonic acid) were significantly and inversely associated only with retrieved oocyte number, selected serum FA were associated with a broad range of pre-fertilization and post-fertilization parameters. Associations of BMI and FF FA were complex, as arachidonic acid was inversely associated with both BMI and retrieved oocyte number, while oleic acid (OA) was directly associated with BMI and PBF. Ultrasound-assessed clinical pregnancy outcome (CP) was directly associated with serum OA but inversely with its trans isomer elaidic acid (EA) and with BMI. Compounded BMI, serum EA and OA discriminated CP well (AUC = 0.74). Whole blood DNA methylation was significantly associated with and a moderate predictor (AUC = 0.66) of percent fertilized oocytes. CONCLUSIONS: Overall FF FA pool composition rather than FA identity may impact oocyte production and cellular memory of FF FA is lost as the oocyte exits the follicular environment. The contrasting associations of BMI, FF OA and arachidonic acid suggest that the control of oocyte homeostasis by FF FA is uncoupled from BMI. Further studies are warranted to assess the potential of compounding BMI with serum EA and OA to predict CP.

Chronic arthritides and bone structure: focus on rheumatoid arthritis-an update.

Normal bone remodeling depends of a balance between bone forming cells, osteoblasts and bone resorbing cells, the osteoclasts. In chronic arthritides and some inflammatory and autoimmune diseases such as rheumatoid arthritis, there is a great constellation of cytokines produced by pannus that impair bone formation and stimulate bone resorption by inducing osteoclast differentiation and inhibiting osteoblast maturation. Patients with chronic inflammation have multiple causes that lead to low bone mineral density, osteoporosis and a high risk of fracture including circulating cytokines, impaired mobility, chronic administration of glucocorticoids, low vitamin D levels and post-menopausal status in women, among others. Biologic agents and other therapeutic measures to reach prompt remission might ameliorate these deleterious effects. In many cases, bone acting agents need to be added to conventional treatment to reduce the risk of fractures and to preserve articular integrity and independency for daily living activities. A limited number of studies related to fractures in chronic arthritides were published, and future investigation is needed to determine the risk of fractures and the protective effects of different treatments to reduce this risk.

Study of turbulent transport in magnetized plasmas with flow using symplectic maps.

Turbulent transport in a magnetized plasma of the kind found in tokamaks is modeled by a 2D wave spectrum that allows reduction to a symplectic map. The properties of particle transport when chaos sets in are analyzed in various circumstances including finite Larmor radius (FLR) effects and a background plasma flow. For large wave amplitudes, regular particle orbits become chaotic, which represents a type of Lagrangian turbulence. When chaos becomes global, it leads to the loss of particle confinement. Poloidal flows tend to decrease the chaos in some regions, and they can give rise to the formation of transport barriers. FLR effects not only reduce chaos but also give rise to non-local behavior. Thus, when the particles have a thermal distribution of Larmor radii, a non-Gaussian particle distribution function in space is obtained. However, the transport preserves its diffusive scaling when there is no flow. Previous results about the dependence of the diffusion coefficient with amplitude are re-derived analytically and numerically taking into account FLR effects. In the presence of general poloidal flows, the transport has to be described by a two-step map. They modify the nature of transport in the direction of the flow from diffusive to ballistic to super-ballistic, depending on the type of flow. The transverse transport, in turn, shows suppression of the oscillations with wave amplitude that are present in the absence of flow. When the plasma flow varies linearly with radius, the transport can be studied with a similar single-step map, and the transverse diffusion coefficient is reduced while parallel transport can become super-ballistic. For non-monotonic flows, there are accelerating modes that can produce ballistic-like particles while the bulk of the particles behaves diffusively.

Diagnosis and Study of Mechanical Vibrations in Cargo Vehicles Using ISO 2631-1:1997.

This study presents the design and implementation of an electronic system aimed at capturing vibrations produced during truck operation. The system employs a graphical interface to display vibration levels, ensuring the necessary comfort and offering indicators as a solution to mitigate the damage caused by these vibrations. Additionally, the system alerts the driver when a mechanical vibration that could potentially impact their health is detected. The field of health is rigorously regulated by various international standards and guidelines. The case of mechanical vibrations, particularly those transmitted to the entire body of a seated individual, is no exception. Internationally, ISO 2631-1:1997/Amd 1:2010 oversees this study. The system was designed and implemented using a blend of hardware and software. The hardware components comprise a vibration sensor, a data acquisition card, and a graphical user interface (GUI). The software components consist of a data acquisition and processing library, along with a GUI development framework. The system underwent testing in a controlled environment and demonstrated stability and robustness. The GUI proved to be intuitive and could be integrated into modern vehicles with built-in displays. The findings of this study suggest that the proposed system is a viable and effective method for capturing vibrations in trucks and informing drivers about vibration levels. This system has the potential to enhance the comfort and safety of truck drivers.

Exploring the Non-Covalent Bonding in Water Clusters.

QTAIM and source function analysis were used to explore the non-covalent bonding in twelve different water clusters (H2O)n obtained by considering n = 2-7 and various geometrical arrangements. A total of seventy-seven O-H⋯O hydrogen bonds (HBs) were identified in the systems under consideration, and the examination of the electron density at the bond critical point (BCP) of these HBs revealed the existence of a great diversity of O-H⋯O interactions. Furthermore, the analysis of quantities, such as |V(r)|/G(r) and H(r), allowed a further description of the nature of analogous O-H⋯O interactions within each cluster. In the case of 2-D cyclic clusters, the HBs are nearly equivalent between them. However, significant differences among the O-H⋯O interactions were observed in 3-D clusters. The assessment of the source function (SF) confirmed these findings. Finally, the ability of SF to decompose the electron density (ρ) into atomic contributions allowed the evaluation of the localized or delocalized character of these contributions to ρ at the BCP associated to the different HBs, revealing that weak O-H⋯O interactions have a significant spread of the atomic contributions, whereas strong interactions have more localized atomic contributions. These observations suggest that the nature of the O-H⋯O hydrogen bond in water clusters is determined by the inductive effects originated by the different spatial arrangements of the water molecules in the studied clusters.

Metabolic Responses of the Microalga Neochloris oleoabundans to Extracellular Self- and Nonself-DNA.

Stressed organisms identify intracellular molecules released from damaged cells due to trauma or pathogen infection as components of the innate immune response. These molecules called DAMPs (Damage-Associated Molecular Patterns) are extracellular ATP, sugars, and extracellular DNA, among others. Animals and plants can recognize their own DNA applied externally (self-exDNA) as a DAMP with a high degree of specificity. However, little is known about the microalgae responses to damage when exposed to DAMPs and specifically to self-exDNAs. Here we compared the response of the oilseed microalgae Neochloris oleoabundans to self-exDNA, with the stress responses elicited by nonself-exDNA, methyl jasmonate (MeJA) and sodium bicarbonate (NaHCO3). We analyzed the peroxidase enzyme activity related to the production of reactive oxygen species (ROS), as well as the production of polyphenols, lipids, triacylglycerols, and phytohormones. After 5 min of addition, self-exDNA induced peroxidase enzyme activity higher than the other elicitors. Polyphenols and lipids were increased by self-exDNA at 48 and 24 h, respectively. Triacylglycerols were increased with all elicitors from addition and up to 48 h, except with nonself-exDNA. Regarding phytohormones, self-exDNA and MeJA increased gibberellic acid, isopentenyladenine, and benzylaminopurine at 24 h. Results show that Neochloris oleoabundans have self-exDNA specific responses.

Extracellular Self- and Non-Self DNA Involved in Damage Recognition in the Mistletoe Parasitism of Mesquite Trees.

Psittacanthus calyculatus parasitizes mesquite trees through a specialized structure called a haustorium, which, in the intrusive process, can cause cellular damage in the host tree and release DAMPs, such as ATP, sugars, RNA, and DNA. These are highly conserved molecules that primarily function as signals that trigger and activate the defense responses. In the present study, we generate extracellular DNA (exDNA) from mesquite (P. laevigata) tree leaves (self-exDNA) and P. calyculatus (non-self exDNA) mistletoe as DAMP sources to examine mesquite trees' capacity to identify specific self or non-self exDNA. We determined that mesquite trees perceive self- and non-self exDNA with the synthesis of O2•-, H2O2, flavonoids, ROS-enzymes system, MAPKs activation, spatial concentrations of JA, SA, ABA, and CKs, and auxins. Our data indicate that self and non-self exDNA application differs in oxidative burst, JA signaling, MAPK gene expression, and scavenger systems. This is the first study to examine the molecular biochemistry effects in a host tree using exDNA sources derived from a mistletoe.

Environmental and biological monitoring of organochlorine pesticides in the city of Salamanca, Mexico.

The former Tekchem Industrial Unit located in the city of Salamanca, Mexico, constitutes an environmental liability in which the presence of high levels of organochlorine pesticides (OCPs) has been reported. In the present study, levels of OCPs were quantified using gas chromatography-mass spectrometry in 52 soil samples and in 88 blood samples from school-age children in the city of Salamanca. A median concentration of 70.6 ng/g (6.93-3299) was obtained for total OCPs in soil, while for the total sum of dichlorodiphenyltrichloroethane (DDT) the value was 49.6 ng/g (6.93-3276). In children, the median level of the total sum of OCPs was 390 ng/g lipid (7.34-14,895), and for the total sum of DDT was 175 ng/g lipid (< LOD-14,802). The OCPs that resulted in highest concentrations in soil were DDT and its metabolites, as well as aldrin and heptachlor epoxide, while in blood the highest levels corresponded to 4,4'-dichlorodiphenyltrichloroethane (4,4'-DDT) and its metabolites, followed by heptachlor and heptachlor epoxide. The spatial distribution of the concentrations of OCPs in soil shows that the facilities of Tekchem may be a significant potential source for the dispersion of these compounds toward the metropolitan area of Salamanca. The results obtained in the present study demonstrate the presence of OCPs in soil and in child population, providing important bases to study the problem from a broader perspective, while reiterating the importance of continuing efforts to generate resolute and precautionary measures with respect to the environmental liability of Tekchem.

Estimation of body weight using body measurements in female water buffaloes reared in southeastern Mexico.

Buffalo farming is an important livestock activity in Mexico. However, the low technological level of the farms makes it difficult to monitor the growth rates of the animals. The objectives of this study were to analyse the body measurements of 107 adult female Murrah buffaloes, to estimate the interrelationships between those measurements and body weight, and to develop equations to predict body weight (BW) using body measurements including withers at height (WH), rump height (RH), body height (BH), heart girth (HG), abdominal girth (AG), pelvic girth (PG), body length (BL), girth circumference (GC), diagonal body length (DBL), pelvic circumference (PC), and abdomen circumference (AC). The study was conducted on two commercial farms in southern Mexico. Pearson correlation and stepwise regression techniques were used for the data analysis. To find out the best regression models, we used model quality criteria such as coefficient of determination (R2), adjusted R2 (Adj.R2), root mean square error (RMSE), Mallow's Cp, Akaike's information criteria (AIC), Bayesian information criteria (BIC), and coefficient of variation (CV). Correlation results indicated that BW had a positive high correlation (P < 0.01) of all the measured traits. Model 4 (-780.56 + 311.76GC + 383.51DBL + 51.82PC + 47.65AC-106.78BL) was the best regression model with a higher R2 (0.87), Adj. R2 (0.86) smaller Cp (4.24), AIC (749.19), BIC (752.16), and RMSE (36.91). The current study suggests that GC, DBL, PC, AC, and BL might be used in combination to estimate BW of adult female Murrah buffaloes.

Human Protein-l-isoaspartate O-Methyltransferase Domain-Containing Protein 1 (PCMTD1) Associates with Cullin-RING Ligase Proteins.

The spontaneous l-isoaspartate protein modification has been observed to negatively affect protein function. However, this modification can be reversed in many proteins in reactions initiated by the protein-l-isoaspartyl (d-aspartyl) O-methyltransferase (PCMT1). It has been hypothesized that an additional mechanism exists in which l-isoaspartate-damaged proteins are recognized and proteolytically degraded. Herein, we describe the protein-l-isoaspartate O-methyltransferase domain-containing protein 1 (PCMTD1) as a putative E3 ubiquitin ligase substrate adaptor protein. The N-terminal domain of PCMTD1 contains l-isoaspartate and S-adenosylmethionine (AdoMet) binding motifs similar to those in PCMT1. This protein also has a C-terminal domain containing suppressor of cytokine signaling (SOCS) box ubiquitin ligase recruitment motifs found in substrate receptor proteins of the Cullin-RING E3 ubiquitin ligases. We demonstrate specific PCMTD1 binding to the canonical methyltransferase cofactor S-adenosylmethionine (AdoMet). Strikingly, while PCMTD1 is able to bind AdoMet, it does not demonstrate any l-isoaspartyl methyltransferase activity under the conditions tested here. However, this protein is able to associate with the Cullin-RING proteins Elongins B and C and Cul5 in vitro and in human cells. The previously uncharacterized PCMTD1 protein may therefore provide an alternate maintenance pathway for modified proteins in mammalian cells by acting as an E3 ubiquitin ligase adaptor protein.