Optimizando el manejo de la uveítis con agentes biológicos en Chile del 2020 / Optimizing uveitis management with biological agents in Chile in 2020

Los agentes biológicos han irrumpido como una alternativa eficaz en el tratamiento de las uveítis no-infecciosas, especialmente en cuadros refractarios a inmunosupresores convencionales, con buena tolerancia y rápido efecto. Hay patologías como la enfermedad de Behçet en que incluso pueden estar indicados como tratamiento de primera línea. Este artículo ayudará a reconocer las patologías específicas donde presentan mayor eficacia, entrega herramientas para escoger el agente más adecuado para cada paciente y sugiere estrategias para evitar la pérdida de control de la enfermedad en el largo plazo.

Biological therapies have emerged as an effective option for the treatment of non-infectious uveitis, especially in refractive cases to conventional immunosup-pressive drugs. They are fast-acting, well tolerated, and can be considered as first-line agents for the treatment of certain uveitis like in Behçet ́s disease. This article will aid in identifying the uveitis syndromes where biological therapy is more effective, help choosing the most appropriate agent for a particular case and offer suggestions on how to keep long-term disease control.

Tumor suppressor Interferon Regulatory Factor 1 selectively blocks expression of endogenous retrovirus.

Endogenous retroviruses (ERVs) comprise 10% of the genome, with many of these transcriptionally silenced post early embryogenesis. Several stimuli, including exogenous virus infection and cellular transformation can reactivate ERV expression via a poorly understood mechanism. We identified Interferon Regulatory Factor 1 (IRF-1), a tumor suppressor and an antiviral host factor, as a suppressor of ERV expression. IRF-1 decreased expression of a specific mouse ERV in vitro and in vivo. IRF-3, but not IRF-7, also decreased expression of distinct ERV families, suggesting that suppression of ERVs is a relevant biological function of the IRF family. Given the emerging appreciation of the physiological relevance of ERV expression in cancer, IRF-1-mediated suppression of specific ERVs may contribute to the overall tumor suppressor activity of this host factor.

Organic matter geochemical signatures (TOC, TN, C/N ratio, δ13C and δ15N) of surface sediment from lakes distributed along a climatological gradient on the western side of the southern Andes.

Paleolimnological studies in western South America, where meteorological stations are scarce, are critical to obtain more realistic and reliable regional reconstructions of past climate and environmental changes, including vegetation and water budget variability. However, climate and environmental geochemical indicators must be tested before they can be applied with confidence. Here we present a survey of lacustrine surface sediment (core top, 0 to ~1cm) biogeochemical proxies (total organic carbon [TOC], total nitrogen [TN], carbon/nitrogen ratio [C/N ratio] and bulk organic δ13C and total δ15N) from a suite of 72 lakes spanning the transition from a Mediterranean climate with a patchwork of cultivated vegetation, pastureland, and conifers in central Chile to a rainy temperate climate dominated by broadleaf deciduous and evergreen forest further south. Sedimentary data are compared to the latitudinal and orographic climatic trends of the region based on the climatology (precipitation and temperature) produced with Climate Forecast System Reanalysis (CFSR) data and the modern Southern Hemisphere Westerly Winds (SWW) location. The geochemical data show inflection points at ~42°S latitude and ~1500m elevation that are likely related to the northern limit of influence of the SWW and elevation of the snow line, respectively. Overall the organic proxies were able to mimic climatic trends (Mean Annual Precipitation [MAP] and temperature [MAT]), indicating that they are a useful tool to be included in paleoclimatological reconstruction of the region.

The pancreatitis-associated protein VMP1, a key regulator of inducible autophagy, promotes Kras(G12D)-mediated pancreatic cancer initiation.

Both clinical and experimental evidence have firmly established that chronic pancreatitis, in particular in the context of Kras oncogenic mutations, predisposes to pancreatic ductal adenocarcinoma (PDAC). However, the repertoire of molecular mediators of pancreatitis involved in Kras-mediated initiation of pancreatic carcinogenesis remains to be fully defined. In this study we demonstrate a novel role for vacuole membrane protein 1 (VMP1), a pancreatitis-associated protein critical for inducible autophagy, in the regulation of Kras-induced PDAC initiation. Using a newly developed genetically engineered model, we demonstrate that VMP1 increases the ability of Kras to give rise to preneoplastic lesions, pancreatic intraepithelial neoplasias (PanINs). This promoting effect of VMP1 on PanIN formation is due, at least in part, by an increase in cell proliferation combined with a decrease in apoptosis. Using chloroquine, an inhibitor of autophagy, we show that this drug antagonizes the effect of VMP1 on PanIN formation. Thus, we conclude that VMP1-mediated autophagy cooperate with Kras to promote PDAC initiation. These findings are of significant medical relevance, molecules targeting autophagy are currently being tested along chemotherapeutic agents to treat PDAC and other tumors in human trials.

Epigenetic regulation of ID4 in the determination of the BRCAness phenotype in breast cancer.

BRCAness breast tumors represent a group of sporadic tumors characterized by a reduction in BRCA1 gene expression. As BRCA1 is involved in double-strand breaks (DSBs) repair, dysfunctional BRCA pathway could make a tumor sensitive to DNA damaging drugs (e.g., platinum agents). Thus, accurately identifying BRCAness could contribute to therapeutic decision making in patients harboring these tumors. The purpose of this study was to identify if BRCAness tumors present a characteristic methylation profile and/or were related to specific clinico-pathological features. BRCAness was measured by MLPA in 63 breast tumors; methylation status of 98 CpG sites within 84 cancer-related genes was analyzed by MS-MLPA. Protein and mRNA expressions of the selected genes were measured by quantitative real-time PCR and Western Blot. BRCAness was associated with younger age, higher nuclear pleomorphism, and triple-negative (TN) status. Epigenetically, we found that the strongest predictors for BRCAness tumors were the methylations of MLH1 and PAX5 plus the unmethylations of CCND2 and ID4. We determined that ID4 unmethylation correlated with the expression levels of both its mRNA and protein. We observed an inverse relation between the expressions of ID4 and BRCA1. To the best of our knowledge, this is the first report suggesting an epigenetic regulation of ID4 in BRCAness tumors. Our findings give new information of BRCAness etiology and encourage future studies on potential drug targets for BRCAness breast tumors.

Genetic inactivation of the pancreatitis-inducible gene Nupr1 impairs PanIN formation by modulating Kras(G12D)-induced senescence.

Nuclear protein 1 (Nupr1), a small chromatin protein, has a critical role in cancer development, progression and resistance to therapy. Previously, we had demonstrated that Nupr1 cooperates with Kras(G12D) to induce pancreas intraepithelial neoplasias (PanIN) formation and pancreatic ductal adenocarcinoma development in mice. However, the molecular mechanisms by which Nupr1 influences Kras-mediated preneoplastic growth remain to be fully characterized. In the current study, we report evidence supporting a role for Nupr1 as a gene modifier of Kras(G12D)-induced senescence, which must be overcome to promote PanIN formation. We found that genetic inactivation of Nupr1 in mice impairs Kras-induced PanIN, leading to an increase in ß-galactosidase-positive cells and an upregulation of surrogate marker genes for senescence. More importantly, both of these cellular and molecular changes are recapitulated by the results of mechanistic experiments using RNAi-based inactivation of Nupr1 in human pancreatic cancer cell models. In addition, the senescent phenotype, which results from Nupr1 inactivation, is accompanied by activation of the FoxO3a-Skp2-p27(Kip1)-pRb-E2F pathway in vivo and in vitro. Thus, combined, these results show, for the first time, that Nupr1 aids oncogenic Kras to bypass senescence in a manner that cooperatively promotes PanIN formation. Besides its mechanistic importance, this new knowledge bears medical relevance as it delineates early pathobiological events that may be targeted in the future as a means to interfere with the formation of preneoplastic lesions early during pancreatic carcinogenesis.

Summer rainfall variability in European Mediterranean mountains from the sixteenth to the twentieth century reconstructed from tree rings.

Since the end of the last glacial period, European Mediterranean mountains have provided shelter for numerous species of Eurosiberian and Boreal origin. Many of these species, surviving at the southern limit of their range in Europe and surrounded by Mediterranean ones, are relatively intolerant to summer drought and are in grave danger of loss, as a result of increasingly long and frequent droughts in this region. This is the case of the Scots pine (Pinus sylvestris) and the Austrian pine (Pinus nigra ssp. salzmannii) which are found on Central Iberian Peninsula at the edge of their natural range. We used a tree ring network of these two species to reconstruct past variations in summer rainfall. The reconstruction, based upon a tree ring composite chronology of the species, dates back to 1570 (adjusted R(2) = 0.49, P < 0.000001) and captures interannual to decadal scale variability in summer precipitation. We studied the spatial representativeness of the rainfall patterns and described the occurrence rate of extremes of this precipitation. To identify associations between macroclimatic factors and tree radial growth, we employed a principal component analysis to calculate the resultant of the relationship between the growth data of both species, using this resultant as a dependent variable of a multiple regression whose independent variables are monthly mean temperature and precipitation from the average records. Spatial correlation patterns between instrumental precipitation datasets for southern Europe and reconstructed values for the 1950-1992 period indicate that the reconstruction captures the regional signal of drought variability in the study region (the origin of this precipitation is convective: thermal low pressure zones induced in the inland northeastern areas of the Iberian Peninsula). There is a clear increase in the recurrence of extreme dry events as from the beginning of twentieth century and an abrupt change to drier conditions. There appears to be a tendency toward recurrent exceptionally dry summers, which could involve a significant change for the Eurosiberian refugee species.

Palladin promotes invasion of pancreatic cancer cells by enhancing invadopodia formation in cancer-associated fibroblasts.

The stromal compartment surrounding epithelial-derived pancreatic tumors is thought to have a key role in the aggressive phenotype of this malignancy. Emerging evidence suggests that cancer-associated fibroblasts (CAFs), the most abundant cells in the stroma of pancreatic tumors, contribute to the tumor's invasion, metastasis and resistance to therapy, but the precise molecular mechanisms that regulate CAFs behavior are poorly understood. In this study, we utilized immortalized human pancreatic CAFs to investigate molecular pathways that control the matrix-remodeling and invasion-promoting activity of CAFs. We showed previously that palladin, an actin-associated protein, is expressed at high levels in CAFs of pancreatic tumors and other solid tumors, and also in an immortalized line of human CAFs. In this study, we found that short-term exposure of CAFs to phorbol esters reduced the number of stress fibers and triggered the appearance of individual invadopodia and invadopodial rosettes in CAFs. Molecular analysis of invadopodia revealed that their composition resembled that of similar structures (that is, invadopodia and podosomes) described in other cell types. Pharmacological inhibition and small interfering RNA knockdown experiments demonstrated that protein kinase C, the small GTPase Cdc42 and palladin were necessary for the efficient assembly of invadopodia by CAFs. In addition, GTPase activity assays showed that palladin contributes to the activation of Cdc42. In mouse xenograft experiments using a mixture of CAFs and tumor cells, palladin expression in CAFs promoted the rapid growth and metastasis of human pancreatic tumor cells. Overall, these results indicate that high levels of palladin expression in CAFs enhance their ability to remodel the extracellular matrix by regulating the activity of Cdc42, which in turn promotes the assembly of matrix-degrading invadopodia in CAFs and tumor cell invasion. Together, these results identify a novel molecular signaling pathway that may provide new molecular targets for the inhibition of pancreatic cancer metastasis.

Platelets: bridging hemostasis, inflammation, and immunity.

Although the function of platelets in the maintenance of hemostasis has been studied in great detail, more recent evidence has highlighted a central role for platelets in the host inflammatory and immune responses. Platelets by virtue of their large numbers and their ability to rapidly release a broad spectrum of immunomodulatory cytokines, chemokines, and other mediators act as circulating sentinels. Upon detection of a pathogen, platelets quickly activate and begin to drive the ensuing inflammatory response. Platelets have the ability to directly modulate the activity of neutrophils (phagocytosis, oxidative burst), endothelium (adhesion molecule and chemokine expression), and lymphocytes. Due to their diverse array of adhesion molecules and preformed chemokines, platelets are able to adhere to leukocytes and facilitate their recruitment to sites of tissue damage or infection. Furthermore, platelets directly participate in the capture and sequestration of pathogens within the vasculature. Platelet-neutrophil interactions are known to induce the release of neutrophil extracellular traps (NETs) in response to either bacterial or viral infection, and platelets have been shown to internalize pathogens, sequestering them in engulfment vacuoles. Finally, emerging data indicate that platelets also participate in the host immune response by directly killing infected cells. This review will highlight the central role platelets play in the initiation and modulation of the host inflammatory and immune responses.

Biomonitoring of antioxidant and oxidative stress responses in Perinereis gualpensis (Polychaeta: Nereididae) in Chilean estuarine regions under different anthropogenic pressure.

This study aimed to analyze oxidative stress parameters, including levels of the antioxidant glutathione (GSH), activity of glutamate-cysteine ligase (GCL) and glutathione-S-transferase (GST), total antioxidant capacity and protein oxidation, in the polychaete Perinereis gualpensis (Nereididae) collected from the Biobío, Itata, Valdivia and Lingue estuaries in Chile, which present different degrees of anthropogenic pressure. Sampling sites were characterized considering a geographic information system and the physicochemical characteristics of water and sediment. Significant differences (p<0.05) were observed between the sampling sites for most of the responses (GSH, GCL, GST and antioxidant capacity), mainly related to human activities such as agriculture, industry, among others. Multivariate correlation analysis indicates a certain relationship of antioxidant responses with human activities, salinity, and worm weight, this last employed to standardize GST and antioxidant capacity. These results clearly indicate biomarker responses in P. gualpensis in Biobío and Valdivia estuaries, the more affected by human activities.

Effects of pulp and paper mill effluents on the microplankton and microbial self-purification capabilities of the Biobío River, Chile.

Most studies focus on the ecotoxicity of pulp and paper mill effluents, rather than on how they affect the physicochemical and biological structure and the intrinsic ecological capabilities of the receiving watercourses. We investigated the impact of such effluents on the water quality, microplankton system and microbial self-purification capacity (degradation of polymeric organic compounds via extracellular enzymes) of the Biobío River in Chile. The physicochemical impact on the water quality was indicated by raised conductivity, by the pollution of the water body with nitrate, nitrite and soluble reactive phosphorus, by the appearance of tannin and lignin, and by the steady accumulation of inorganic and organic suspended matter (SPM) along the river. From the biological structure of the microplankton system, very low and declining concentrations of chlorophyll a and heterotrophic flagellate densities were determined. The pulp and paper mill effluents introduced high bacterial abundances and biomass concentrations into the river water. This reflects the effective use made of the abundantly available inorganic and organic nutrients within this industrial and municipal process water by bacteria adapted to these extreme environments, additionally supported by concomitant low grazing pressure derivable from low heterotrophic flagellate abundances. Indeed, in one section of the river affected by a pulp mill, the plant was found to significantly contribute to the self-cleaning capacity of the river. However, this elevated degradation capacity was not enough to compensate for the additionally discharged organic material which, together with the toxic effects of the paper plant effluents, significantly interferes with the ecological status of the Biobío River.

Environmental evidence of fossil fuel pollution in Laguna Chica de San Pedro lake sediments (Central Chile).

This paper describes lake sediment spheroidal carbonaceous particle (SCP) profiles from Laguna Chica San Pedro, located in the Biobío Region, Chile (36 degrees 51' S, 73 degrees 05' W). The earliest presence of SCPs was found at 16 cm depth, corresponding to the 1915-1937 period, at the very onset of industrial activities in the study area. No SCPs were found at lower depths. SCP concentrations in Laguna Chica San Pedro lake sediments were directly related to local industrial activities. Moreover, no SCPs were found in Galletué lake (38 degrees 41' S, 71 degrees 17.5' W), a pristine high mountain water body used here as a reference site, suggesting that contribution from long distance atmospheric transport could be neglected, unlike published data from remote Northern Hemisphere lakes. These results are the first SCP sediment profiles from Chile, showing a direct relationship with fossil fuel consumption in the region. Cores were dated using the 210Pb technique.

Use of Daphnia spp. for the ecotoxicological assessment of water quality in an agricultural watershed in South-Central Chile.

Because of the importance of surface waters from the Chillán River watershed (Chile) for recreation, agricultural irrigation, and the production of drinking water, local concern about river water quality has increased considerably during the last decade. Agricultural and forestry activities in the watershed, characterized by an intensive use of pesticides, are thought to play an important role in the generation of non-point-source pollution, whereas the discharge of urban wastewater from the city of Chillán constitutes a major point source of pollution. In the present investigation, acute and chronic laboratory bioassays using Daphnia spp. were conducted on surface water samples from 17 river stations located throughout the watershed. Sampling occurred on 6 occasions during a 16-month period (2000 to 2001) and included both high and low flow conditions. Almost all toxic effects observed in summer were directly related to the discharge of urban wastewater, whereas toxicity in rural areas was mainly detected during the winter period when rainfall and river flow are high. Toxicity test results were compared with measured physicochemical water-quality data. Mortality and alterations in reproductive success of Daphnia spp. were not consistently reflected in detected chemical pollution. With only one exception (atrazine), detected pesticide concentrations were below known toxicity levels. However, additive and synergistic effects of the presence of a mixture of pesticides could not be excluded as a possible cause of observed toxicity. At several stations, filtering of the water sample led to a strong decrease in toxicity, which suggests the presence of xenobiotics attached to the smaller sediment fraction. Inclusion of sediment chemical analysis and sediment toxicity testing in future work should therefore be encouraged. The presented approach provided information about the adverse effects of human activities on surface water quality in the watershed, not easily obtained from classical monitoring schemes. In specific cases, the approach may represent an economically attractive alternative to physicochemical analyses. Modifications to the proposed methodology should be introduced if the effects of intrastorm and interstorm variability of water quality are to be analyzed.

Association of distinct alpha(2) adrenoceptor and serotonin transporter polymorphisms with constipation and somatic symptoms in functional gastrointestinal disorders.

BACKGROUND: The role of genetics in the phenotypic manifestations of irritable bowel syndrome (IBS) is unclear. Our aims were: (1) to compare the prevalence of polymorphisms of alpha 2 (alpha(2)) adrenoceptors, norepinephrine transporter, and serotonin transporter protein (soluble carrier protein member 4 (SLC6A4)) promoter in patients with lower functional gastrointestinal disorders (FGID) and in healthy controls; and (2) to test associations of these genetic variations with symptoms of IBS and high somatic symptom scores. METHODS: Validated bowel and somatic symptom questionnaires characterised the phenotype: 90 with IBS constipation (IBS-C), 128 IBS diarrhoea, 38 IBS alternating bowel function, and 20 chronic abdominal pain. Logistic regression analyses assessed associations of different polymorphisms for alpha(2) adrenoceptor and SLC6A4 with IBS or chronic abdominal pain phenotypes and high somatic score. RESULTS: Two distinct polymorphisms independently appeared to be associated with the phenotype IBS-C: alpha(2C) Del 322-325 (odds ratio (OR) 2.48 (95% confidence interval (CI) 0.98, 6.28); p = 0.05) and alpha(2A) -1291 (C-->G) (OR 1.66 (95% CI 0.94, 2.92); p = 0.08) relative to wild-type. Overall, the alpha(2C) Del 322-325 polymorphism (alone or combined with other polymorphisms) was also significantly associated with a high somatic symptom score (OR 2.2 (95% CI 1.06, 4.64); p = 0.03). Combinations of polymorphisms were also associated with high somatic scores. CONCLUSION: Functionally distinct alpha(2A) and alpha(2C) adrenoceptor and serotonin transporter polymorphisms are associated with constipation and high somatic symptoms in patients with lower functional gastrointestinal disorders, although the strength of the genetic contribution to the phenotype is unclear.

[Antitumoral effect of HSV-tk suicide gene associated with ganciclovir in an experimental model of head and neck epidermoid carcinoma]. / Efecto antitumoral del gen suicida HSV-tk y ganciclovir en un modelo experimental de carcinoma epidermoide de cabeza y cuello.

INTRODUCTION: We studied the transfection by adenoviral vectors and the antitumoral effect of HSV-tk gene associated with ganciclovir (AdCMVtk/GCV) in KB human oral cavity squamous cell carcinoma, in vitro and in vivo. MATERIALS AND METHODS: Transfection was assessed by the X-gal stain. It was used in cell cultures and tumoral sections previously exposed to adenoviral vector AdCMVlacZ. In vitro, in order to study the antitumoral effect of AdCMVtk/GCV, survival of cell cultures exposed to AdCMVtk/GCV and to AdCMVlacZ/GCV was compared. In vivo, necrotic volume as a percentage of total tumoral volume, was compared between AdCMVtk/GCV treated group and AdCMVlacZ/GCV exposed group. Hepatic and renal toxicities were assessed. RESULTS: In vitro, survival of cell cultures treated with AdCMVtk/GCV was less than AdCMVlacZ/GCV exposed cells. In vivo, necrotic volume was larger in AdCMVtk/GCV treated group than in AdCMVlacZ/GCV exposed group. No toxicity was found (hepatic, renal). CONCLUSIONS: KB cells are transfected by adenoviral vectors and are killed by AdCMVtk/GCV, both in vitro and in vivo (no toxicity was found in the animal model).

First report on chlorinated pesticide deposition in a sediment core from a small lake in central Chile.

This paper presents a first report on chlorinated pesticide deposition analyzed through sedimentary records in a small mesotrophic lake (Chica de San Pedro) in central Chile. The sediment core was sliced and dated using 210Pb, 137Cs and pollen analyses. Organochlorine pesticides were analyzed by gas chromatography with electron capture detection (GC-ECD). From these results, pesticide deposition over the last 50 years was estimated. No pesticides were detected below the 1940 slice of the core. Concentrations were in the range 0.640-1.4 ng/g d.w. for total DDTs, 0.046-0.362 ng/g d.w. for lindane and 0.015-0.310 ng/g d.w. for alpha-hexachlorohexane. Highest concentrations of pp'DDT were found in 1993-1996 and higher concentrations of pp'-DDE and pp'-DDD were found in the seventies (1972-1978). Total organic carbon (TOC) normalized data were used for statistical analysis. Although significant correlation was observed between concentrations of DDE and DDD, no correlation was found for DDT, suggesting that it had a different source. Factorial analysis grouped DDE together with DDD, while DDT was grouped together with gamma- and alpha-HCH. Total DDT fluxes were highest during the 1970s, while those for HCHs have been increasing in the 1990s. In Chile, organochlorine compounds were banned in 1985, and the historical deposition patterns seem to indicate that such measures have been effective. On the other hand, results point out a relatively new occurrence of pp'-DDT in the watershed, but the source remains unknown.

The Sp1-like protein BTEB3 inhibits transcription via the basic transcription element box by interacting with mSin3A and HDAC-1 co-repressors and competing with Sp1.

Sp1-like proteins are characterized by three conserved C-terminal zinc finger motifs that bind GC-rich sequences found in promoters of numerous genes essential for mammalian cell homeostasis. These proteins behave as transcriptional activators or repressors. Although significant information has been reported on the molecular mechanisms by which Sp1-like activators function, relatively little is known about mechanisms for repressor proteins. Here we report the functional characterization of BTEB3, a ubiquitously expressed Sp1-like transcriptional repressor. GAL4 assays show that the N terminus of BTEB3 contains regions that can act as direct repressor domains. Immunoprecipitation assays reveal that BTEB3 interacts with the co-repressor mSin3A and the histone deacetylase protein HDAC-1. Gel shift assays demonstrate that BTEB3 specifically binds the BTE site, a well characterized GC-rich DNA element, with an affinity similar to that of Sp1. Reporter and gel shift assays in Chinese hamster ovary cells show that BTEB3 can also mediate repression by competing with Sp1 for BTE binding. Thus, the characterization of this protein expands the repertoire of BTEB-like members of the Sp1 family involved in transcriptional repression. Furthermore, our results suggest a mechanism of repression for BTEB3 involving direct repression by the N terminus via interaction with mSin3A and HDAC-1 and competition with Sp1 via the DNA-binding domain.

A conserved alpha-helical motif mediates the interaction of Sp1-like transcriptional repressors with the corepressor mSin3A.

Sp1-like proteins are defined by three highly homologous C(2)H(2) zinc finger motifs that bind GC-rich sequences found in the promoters of a large number of genes essential for mammalian cell homeostasis. Here we report that TIEG2, a transforming growth factor beta-inducible Sp1-like protein with antiproliferative functions, represses transcription through recruitment of the mSin3A-histone deacetylase complex. The interaction of TIEG2 with mSin3A is mediated by an alpha-helical repression motif (alpha-HRM) located within the repression domain (R1) of TIEG2. This alpha-HRM specifically associates with the second paired amphipathic helix (PAH2) domain of mSin3A. Mutations in the TIEG2 alpha-HRM domain that disrupt its helical structure abolish its ability to both bind mSin3A and repress transcription. Interestingly, the alpha-HRM is conserved in both the TIEG (TIEG1 and TIEG2) and BTEB (BTEB1, BTEB3, and BTEB4) subfamilies of Sp1-like proteins. The alpha-HRM from these proteins also mediates direct interaction with mSin3A and represses transcription. Surprisingly, we found that the alpha-HRM of the Sp1-like proteins characterized here exhibits structural and functional resemblance to the Sin3A-interacting domain previously described for the basic helix-loop-helix protein Mad1. Thus, our study defines a mechanism of transcriptional repression via the interactions of the alpha-HRM with the Sin3-histone deacetylase complex that is utilized by at least five Sp1-like transcriptional factors. More importantly, we demonstrate that a helical repression motif which mediates Sin3 interaction is not an exclusive structural and functional characteristic of the Mad1 subfamily but rather has a wider functional impact on transcriptional repression than previously demonstrated.