SMS2, a Novel Allele of OsINV3, Regulates Grain Size in Rice.

Grain size has an important effect on rice yield. Although several key genes that regulate seed size have been reported in rice, their molecular mechanisms remain unclear. In this study, a rice small grain size 2 (sms2) mutant was identified, and MutMap resequencing analysis results showed that a 2 bp insertion in the second exon of the LOC_Os02g01590 gene resulted in a grain length and width lower than those of the wild-type Teqing (TQ). We found that SMS2 encoded vacuolar acid invertase, a novel allele of OsINV3, which regulates grain size. GO and KEGG enrichment analyses showed that SMS2 was involved in endoplasmic reticulum protein synthesis, cysteine and methionine metabolism, and propionic acid metabolism, thereby regulating grain size. An analysis of sugar content in young panicles showed that SMS2 reduced sucrose, fructose, and starch contents, thus regulating grain size. A haplotype analysis showed that Hap2 of SMS2 had a longer grain and was widely present in indica rice varieties. Our results provide a new theoretical basis for the molecular and physiological mechanisms by which SMS2 regulates grain size.

Evaluating the clinical efficacy and safety of concurrent chemoradiotherapy with cisplatin and nab-paclitaxel in postoperative early-stage cervical cancer.

OBJECTIVE: A preclinical study showed that nab-paclitaxel acted as a radiosensitizer and improved tumor radiotherapy in a supra-additive manner. In this study, we aimed to evaluate the clinical efficacy and safety of concurrent chemoradiotherapy (CCRT) with cisplatin and nab-paclitaxel in postoperative early-stage cervical cancer with an unfavorable prognosis. METHODS: Eligible patients with stage IB1-IIA2 (FIGO 2009) cervical carcinoma were recruited retrospectively between August 2018 to May 2021. Patients in both the cisplatin and nab-paclitaxel groups received postoperative radiotherapy and weekly intravenous cisplatin 40 mg/m2 or nab-paclitaxel 100 mg concurrently. An analysis of overall survival, progression-free survival, and adverse reactions was conducted. RESULTS: A total of 105 early-stage cervical cancer patients were included into our study. The median follow-up time was 38.7 months. The 3-year overall survival and progression-free survival in both group was similar. The cycles of chemotherapy in the cisplatin group were less than those in the nab-paclitaxel group (4.5 vs. 5.0; p = 0.001). Patients in the cisplatin group had a significantly higher frequency of hematological adverse events than patients in the nab-paclitaxel group (P < 0.05). Patients in the cisplatin group had a significantly higher frequency of grade 3-4 leukopenia (46.1% vs. 18.9%; P = 0.03), grade 1-2 thrombocytopenia (32.7% vs. 9.5%; P = 0.014) than patients in the nab-paclitaxel group. Gastrointestinal reactions, such as vomiting, nausea, and anorexia were significantly reduced in the nab-paclitaxel group compared with those in the cisplatin group. Regarding the effects on alopecia, the incidence rate of the nab-paclitaxel group was higher than that of the cisplatin group (P = 0.001). There were no differences between the groups in terms of other adverse reactions. CONCLUSION: The results of this study indicate that nab-paclitaxel-based concurrent radiotherapy is tolerable and effective, and can be considered an alternative to cisplatin chemotherapy.

Natural variation in SSW1 coordinates seed growth and nitrogen use efficiency in Arabidopsis.

Seed size is controlled not only by intrinsic genetic factors but also by external environmental signals. Here, we report a major quantitative trait locus (QTL) gene for seed size and weight on chromosome 1 (SSW1) in Arabidopsis, and we found SSW1 acts maternally to positively regulate seed size. Natural variation in SSW1 contains three types of alleles. The SSW1Cvi allele produces larger seeds with more amino acid and storage protein contents than the SSW1Ler allele. SSW1Cvi displays higher capacity for amino acid transport than SSW1Ler due to the differences in transport efficiency. Under low nitrogen supply, the SSW1Cvi allele exhibits increased seed yield and nitrogen use efficiency (NUE). Locations of natural variation alleles of SSW1 are associated with local soil nitrogen contents, suggesting that SSW1 might contribute to geographical adaptation in Arabidopsis. Thus, our findings reveal a mechanism that coordinates seed growth and NUE, suggesting a potential target for improving seed yield and NUE in crops.

A dynamic ubiquitination balance of cell proliferation and endoreduplication regulators determines plant organ size.

Ubiquitination plays a crucial role throughout plant growth and development. The E3 ligase DA2 has been reported to activate the peptidase DA1 by ubiquitination, hereby limiting cell proliferation. However, the molecular mechanisms that regulate DA2 remain elusive. Here, we demonstrate that DA2 has a very high turnover and auto-ubiquitinates with K48-linkage polyubiquitin chains, which is counteracted by two deubiquitinating enzymes, UBIQUITIN-SPECIFIC PROTEASE 12 (UBP12) and UBP13. Unexpectedly, we found that auto-ubiquitination of DA2 does not influence its stability but determines its E3 ligase activity. We also demonstrate that impairing the protease activity of DA1 abolishes the growth-reducing effect of DA2. Last, we show that synthetic, constitutively activated DA1-ubiquitin fusion proteins overrule this complex balance of ubiquitination and deubiquitination and strongly restrict growth and promote endoreduplication. Our findings highlight a nonproteolytic function of K48-linked polyubiquitination and reveal a mechanism by which DA2 auto-ubiquitination levels, in concert with UBP12 and UBP13, precisely monitor the activity of DA1 and fine-tune plant organ size.

Genome-Wide Identification and Expression Analysis of the DA1 Gene Family in Sweet Potato and Its Two Diploid Relatives.

The DA1-like gene family plays a crucial role in regulating seed and organ size in plants. The DA1 gene family has been identified in several species but has not yet been reported in sweet potatoes. In this study, nine, eleven, and seven DA1s were identified in cultivated sweet potato (Ipomoea batatas, 2n = 6x = 90) and its two diploid wild relatives, I. trifida (2n = 2x = 30) and I. triloba (2n = 2x = 30), respectively. The DA1 genes were classified into three subgroups based on their phylogenetic relationships with Arabidopsis thaliana and Oryza sativa (rice). Their protein physiological properties, chromosomal localization, phylogenetic relationships, gene structure, promoter cis-elements, and expression patterns were systematically analyzed. The qRT-PCR results showed that the expression levels of four genes, IbDA1-1, IbDA1-3, IbDA1-6, and IbDA1-7, were higher in the sweet potato leaves than in the roots, fiber roots, and stems. In our study, we provide a comprehensive comparison and further the knowledge of DA1-like genes in sweet potatoes, and provide a theoretical basis for functional studies.

Effects of oxygen vacancies and interfacial strain on the metal-insulator transition of VO2 nanobeams.

The role of oxygen vacancies and interfacial strain on the metal-insulator transition (MIT) behavior of high-quality VO2 nanobeams (NBs) synthesized on SiO2/Si substrates employing V2O5 as a precursor has been investigated in this research. Selective oxygen vacancies have been generated by argon plasma irradiation. The MIT is progressively suppressed as the duration of plasma processing increases; in addition, the temperature of MIT (TMIT) drops by up to 95 K relative to the pristine VO2 NBs. Incorporating oxygen vacancies into VO2 may increase its electron concentration, which might shift the Fermi levels upward, strengthen the electronic orbital overlap of the V-V chains, and further stabilize the metallic phase at lower temperatures, based on first-principles calculations. Furthermore, in order to evaluate the influence of substrate-induced strain in our situation, the MIT in two distinct types of VO2 NB samples is examined without metal contacts by using the distinctive light scattering characteristics of the metal (M) and insulator (I) phases (i.e., M/I domains) by optical microscopy. It is found that the domain structures in the "clamped" NBs persisted up to ∼453 K, while the "released" NBs (transferred to a new substrate) did not exhibit any domain structures and turned into an entirely M phase with a dark contrast above ∼348 K. When combined with first-principles calculations, the electronic orbital occupancy in the rutile phase contributes to explaining the interfacial strain-induced modulation of MIT. The current findings shed light on how interfacial strain and oxygen vacancies impact MIT behavior. It also suggests several types of control strategies for MIT in VO2 NBs, which are essential for a broader spectrum of VO2 NB applications.

Drug-target Affinity Prediction by Molecule Secondary Structure Representation Network.

INTRODUCTION: Identification of drug-target interactions (DTI) is a crucial step in drug development with high specificity and low toxicity. To accelerate the process, computer-aided DTI prediction algorithms have been used to screen compounds or targets rapidly. Furthermore, DTI prediction can be used to identify potential targets for existing drugs, thus uncovering new indications and repositioning them. Therefore, it is of great importance to develop efficient and accurate DTI prediction algorithms. METHOD: Current algorithms usually represent drugs as extracted features, which are learned by convolutional neural networks (CNNs) from its linear representation, or utilize graph neural networks (GNNs) to learn its graph representation. However, these methods either lose information or fail to capture the structural information of the drug. To address this issue, a novel molecule secondary structure representation network (MSSRN) is proposed to learn drug characterization more accurately. Firstly, the network performs relational graph convolutional networks (R-GCNs) on the drug's molecular graph and integrates drug sequence convolutions to learn the sequential information. Secondly, inspired by the attention mechanism, spatial importance weights of the drug sequence are calculated to guide R-GCNs to learn the topological information of the drug. RESULT: A drug-target affinity model, called MSSRN-DTA, was then constructed by using MSSRN to learn drug structure and CNN to learn protein sequence. CONCLUSION: The effectiveness of the proposed method is verified by comparing it with other alternative methods and baseline models on two benchmark datasets.

The cytosolic aminotransferase VAS1 coordinates aromatic amino acid biosynthesis and metabolism.

The aromatic amino acids (AAAs) phenylalanine, tyrosine, and tryptophan are basic protein units and precursors of diverse specialized metabolites that are essential for plant growth. Despite their significance, the mechanisms that regulate AAA homeostasis remain elusive. Here, we identified a cytosolic aromatic aminotransferase, REVERSAL OF SAV3 PHENOTYPE 1 (VAS1), as a suppressor of arogenate dehydrogenase 2 (adh2) in Arabidopsis (Arabidopsis thaliana). Genetic and biochemical analyses determined that VAS1 uses AAAs as amino donors, leading to the formation of 3-carboxyphenylalanine and 3-carboxytyrosine. These pathways represent distinct routes for AAA metabolism that are unique to specific plant species. Furthermore, we show that VAS1 is responsible for cytosolic AAA biosynthesis, and its enzymatic activity can be inhibited by 3-carboxyphenylalanine. These findings provide valuable insights into the crucial role of VAS1 in producing 3-carboxy AAAs, notably via recycling of AAAs in the cytosol, which maintains AAA homeostasis and allows plants to effectively coordinate the complex metabolic and biosynthetic pathways of AAAs.

E3 ligases MAC3A and MAC3B ubiquitinate UBIQUITIN-SPECIFIC PROTEASE14 to regulate organ size in Arabidopsis.

The molecular mechanisms controlling organ size during plant development ultimately influence crop yield. However, a deep understanding of these mechanisms is still lacking. UBIQUITIN-SPECIFIC PROTEASE14 (UBP14), encoded by DA3, is an essential factor determining organ size in Arabidopsis (Arabidopsis thaliana). Here, we identified two suppressors of the da3-1 mutant phenotype, namely SUPPRESSOR OF da3-1 1 and 2 (SUD1 and SUD2), which encode the E3 ligases MOS4-ASSOCIATED COMPLEX 3A (MAC3A) and MAC3B, respectively. The mac3a-1 and mac3b-1 mutations partially suppressed the high ploidy level and organ size phenotypes observed in the da3-1 mutant. Biochemical analysis showed that MAC3A and MAC3B physically interacted with and ubiquitinated UBP14/DA3 to modulate its stability. We previously reported that UBP14/DA3 acts upstream of the B-type cyclin-dependent kinase CDKB1;1 and maintains its stability to inhibit endoreduplication and cell growth. In this work, MAC3A and MAC3B were found to promote the degradation of CDKB1;1 by ubiquitinating UBP14/DA3. Genetic analysis suggests that MAC3A and MAC3B act in a common pathway with UBP14/DA3 to control endoreduplication and organ size. Thus, our findings define a regulatory module, MAC3A/MAC3B-UBP14-CDKB1;1, that plays a critical role in determining organ size and endoreduplication in Arabidopsis.

Comparison of Survival Outcomes in Young Patients With Breast Cancer Receiving Contralateral Prophylactic Mastectomy Versus Unilateral Mastectomy.

BACKGROUND: Contralateral prophylactic mastectomy (CPM) has been performed for several decades in patients with unilateral breast cancer (BC). However, the survival benefits of CPM are controversial, particularly in young women. MATERIALS AND METHOD: In this retrospective study, the clinical total of 69,000 young female patients (age ≤ 40 years) who were diagnosed to have unilateral BC and underwent unilateral mastectomy (UM) or CPM between January 1, 2000 and December 31, 2019 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was performed to minimize selection bias and overcome differences in tumor characteristics between the CPM and UM groups. Overall survival (OS) and BC-specific survival (BCSS) were assessed using Kaplan-Meier curves and compared across groups using log-rank test. Multivariable Cox proportional hazards regression analysis was performed to estimate hazard ratios (HRs). RESULTS: A total of 36,528 patients (21,600 and 14,928 patients in the UM and CPM groups, respectively) were included in follow study. The CPM group showed a higher 5-year OS rate (82.1% vs. 75.8%) and a higher 5-year BCSS rate (83.5% vs. 77.7%) than the UM group. Multivariate Cox analysis after PSM (n = 13,089) showed that CPM significantly decreased 25% risk of all-cause mortality (OS, HR: 0.75, 95% confidence interval [CI]: 0.70-0.80; P < .001) and 25% risk of BC-specific mortality (BCSS, HR: 0.75, 95% CI: 0.70-0.80; P < .001) in young BC patients as compared to UM. CONCLUSION: This study suggests that CPM improved OS and BCSS benefits in young BC patients as compared to UM. Randomized clinical trials with a larger sample size are required in the future to confirm these results.

The SOD7/DPA4-GIF1 module coordinates organ growth and iron uptake in Arabidopsis.

Organ growth is controlled by both intrinsic genetic factors and external environmental signals. However, the molecular mechanisms that coordinate plant organ growth and nutrient supply remain largely unknown. We have previously reported that the B3 domain transcriptional repressor SOD7 (NGAL2) and its closest homologue DPA4 (NGAL3) act redundantly to limit organ and seed growth in Arabidopsis. Here we report that SOD7 represses the interaction between the transcriptional coactivator GRF-INTERACTING FACTOR 1 (GIF1) and growth-regulating factors (GRFs) by competitively interacting with GIF1, thereby limiting organ and seed growth. We further reveal that GIF1 physically interacts with FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR (FIT), which acts as a central regulator of iron uptake and homeostasis. SOD7 can competitively repress the interaction of GIF1 with FIT to influence iron uptake and responses. The sod7-2 dpa4-3 mutant enhances the expression of genes involved in iron uptake and displays high iron accumulation. Genetic analyses support that GIF1 functions downstream of SOD7 to regulate organ and seed growth as well as iron uptake and responses. Thus, our findings define a previously unrecognized mechanism that the SOD7/DPA4-GIF1 module coordinates organ growth and iron uptake by targeting key regulators of growth and iron uptake.

MiR-363 restrain the proliferation, migration and invasion of colorectal carcinoma cell by targeting E2F3.

MicroRNA (miRNA) is associated with tumor cell proliferation, migration and invasion. Studies have shown that miRNAs are closely related to the occurrence and development of colorectal cancer (CRC), but the mechanisms deserve further investigation. In this study, we aim to explore the role of miR-363 on CRC tumorigenesis. Using CRC cell lines, we tested the expression of miR-363 by using RT-PCR, and miR-363 effect on cell behavior was test by using CCK-8 assay, wound-healing assay and cell invasion assay, and western blotting. Luciferase reporter assay and western blot confirmed that E2F3 was the target gene for miR-363. We further examined the effect of E2F3 on the regulation of miR-363 on cell behavior through knockdown of E2F3. Western blot and RT-PCR assay showed that miR-363 inhibited the expression of E2F3 in HCT-116 and SW480 cell. MiR-363 overexpression or E2F3 knockdown inhibited cell proliferation, migration and invasion of CRC. This study demonstrated that miR-363 is able to suppress cell proliferation, migration and invasion by negative regulating E2F3 in CRC cells, and inhibits tumor growth in vivo.

Clinicopathological characteristics and survival outcomes in patients with angiosarcoma of breast.

BACKGROUND: Angiosarcoma of the breast is a rare malignancy. There are little data evaluating the survival and estimating the prognostic factors. The best surgical management and the role of systemic adjuvant therapy remain ill-defined. This study aimed to investigate the clinicopathological features, survival, and prognostic factors of breast angiosarcoma. METHODS: The data on patients diagnosed with breast angiosarcoma were extracted from the Surveillance, Epidemiology, and End Results database (1975-2016). Univariate and multivariate Cox regression analyses were used to estimate the influential prognostic factors. The overall survival (OS) and disease-specific survival (DSS) of patients with breast angiosarcoma were evaluated. RESULTS: This study included 656 patients diagnosed with breast angiosarcoma between 1975 and 2016. The 5-year OS rate of all patients was 44.9% (95% CI 40.8-49.0). In both OS and DSS, Kaplan-Meier survival analyses revealed significant differences for both OS and DSS according to age, year at diagnosis, laterality, grade, and stage (all log-rank p < 0.05). Multivariate analysis suggested that lesions of the right breast, poor differentiation, and advanced stage were independent risk factors for OS or DSS (all p < 0.05). Older age was a risk factor in OS, but was protective in DSS. In primary breast angiosarcoma, age, laterality, grade, and stage were independent prognostic factors in OS and DSS (all p < 0.05). Mastectomy was also a risk factor in DSS (p = 0.034). The proportion of patients with grade III and regional disease was larger in the mastectomy group. CONCLUSION: Angiosarcoma of the breast had a poor prognosis. In our study, age, laterality, histologic grade, and stage were identified as significant prognostic factors. Why patients with angiosarcoma of the right breast had a worse prognosis remains equivocal. Mastectomy was adopted more often by surgeons in this cohort study for patients with advanced primary breast angiosarcoma.

Gate-Tunable van der Waals Photodiodes with an Ultrahigh Peak-to-Valley Current Ratio.

Photodetectors and imagers based on 2D layered materials are currently subject to a rapidly expanding application space, with an increasing demand for cost-effective and lightweight devices. However, the underlying carrier transport across the 2D homo- or heterojunction channel driven by the external electric field, like a gate or drain bias, is still unclear. Here, a visible-near infrared photodetector based on van der Waals stacked molybdenum telluride (MoTe2 ) and black phosphorus (BP) is reported. The type-I and type-II band alignment can be tuned by the gate and drain voltage combined showing a dynamic modulation of the conduction polarity and negative differential transconductance. The heterojunction devices show a good photoresponse to light illumination ranging from 520-2000 nm. The built-in potential at the MoTe2 /BP interface can efficiently separate photoexcited electron-hole pairs with a high responsivity of 290 mA W-1 , an external quantum efficiency of 70%, and a fast photoresponse of 78 µs under zero bias.

Control of lateral root initiation by DA3 in Arabidopsis.

Lateral root (LR) initiation is controlled by the pericycle and the neighboring endodermis in Arabidopsis. Here, we demonstrate that UBIQUITIN-SPECIFIC PROTEASE14/DA3 regulates LR initiation by modulating auxin signaling in the pericycle and endodermis. DA3 negatively affects the mRNA and protein levels of AUXIN RESPONSE FACTOR7 (ARF7) and ARF19 in the pericycle and endodermis but positively regulates the protein stability of SHORT HYPOCOTYL 2 (SHY2/IAA3), an auxin signaling repressor, in the endodermis. We show that DA3 interacts with ARF7 and ARF19, inhibiting their binding to the locus of LATERAL ORGAN BOUNDARY DOMAIN16 (LBD16) to repress its expression in the pericycle. SHY2 also interacts with ARF7 and ARF19 in the endodermis and enhances the DA3 repressive effect on ARF7 and ARF19, thus modulating LBD16 expression in the pericycle. Overall, our findings show that DA3 acts with SHY2, ARF7, and ARF19 to coordinate auxin signaling in the pericycle and endodermis to control LR initiation in Arabidopsis.

Baicalin Blocks Colon Cancer Cell Cycle and Inhibits Cell Proliferation through miR-139-3p Upregulation by Targeting CDK16.

Baicalin was reported to facilitate the apoptosis of colon cells and inhibit tumor growth in vivo. This study aimed to explore the specific mechanism and function of baicalin on colon cells. Relative mRNA levels were tested via qPCR. Cell proliferation, viability, and cell cycle phases were evaluated using MTT, colony formation, and flow cytometry assays, respectively. The interaction between miR-139-3p and cyclin-dependent kinase 16 (CDK16) was measured via a dual-luciferase reporter assay. Immunohistochemistry was used to count the positivity cells in tumor tissues collected from treated xenografted tumor mice. The results showed that baicalin increased miR-139-3p expression while also decreasing CDK16 levels, blocking the cell cycle, and inhibiting cell proliferation in colon cancer cells. miR-139-3p silencing or CDK16 overexpression abolished the inhibitory effects of baicalin on colon cancer proliferation. miR-139-3p directly targeted and interacted with CDK16 at the cellular level. The protective functions of miR-139-3p knockdown on tumor cells were abrogated by silencing CDK16. The combination of baicalin treatment and CDK16 knockdown further inhibited tumor growth of xenografted tumor mice compared with the groups injected with only sh-CDK16 or baicalin in vivo. In conclusion, baicalin inhibited colon cancer growth by modulating the miR-139-3p/CDK16 axis.

OsFTL12, a member of FT-like family, modulates the heading date and plant architecture by florigen repression complex in rice.

FLOWERING LOCUS T (FT), a florigen in Arabidopsis, plays critical roles in floral transition. Among 13 FT-like members in rice, OsFTL2 (Hd3a) and OsFTL3 (RFT1), two rice homologues of FT, have been well characterized to act as florigens to induce flowering under short-day (SD) and long-day (LD) conditions, respectively, but the functions of other rice FT-like members remain largely unclear. Here, we show that OsFTL12 plays an antagonistic function against Hd3a and RFT1 to modulate the heading date and plant architecture in rice. Unlike Hd3a and RFT1, OsFTL12 is not regulated by daylength and highly expressed in both SD and LD conditions, and delays the heading date under either SD or LD conditions. We further demonstrate that OsFTL12 interacts with GF14b and OsFD1, two key components of the florigen activation complex (FAC), to form the florigen repression complex (FRC) by competing with Hd3a for binding GF14b. Notably, OsFTL12-FRC can bind to the promoters of the floral identity genes OsMADS14 and OsMADS15 and suppress their expression. The osmads14 osmads15 double mutants could not develop panicles and showed erect leaves. Taken together, our results reveal that different FT-like members can fine-tune heading date and plant architecture by regulating the balance of FAC and FRC in rice.

An endoplasmic reticulum-associated degradation-related E2-E3 enzyme pair controls grain size and weight through the brassinosteroid signaling pathway in rice.

Grain size is an important agronomic trait, but our knowledge about grain size determination in crops is still limited. Endoplasmic reticulum (ER)-associated degradation (ERAD) is a special ubiquitin proteasome system that is involved in degrading misfolded or incompletely folded proteins in the ER. Here, we report that SMALL GRAIN 3 (SMG3) and DECREASED GRAIN SIZE 1 (DGS1), an ERAD-related E2-E3 enzyme pair, regulate grain size and weight through the brassinosteroid (BR) signaling pathway in rice (Oryza sativa). SMG3 encodes a homolog of Arabidopsis (Arabidopsis thaliana) UBIQUITIN CONJUGATING ENZYME 32, which is a conserved ERAD-associated E2 ubiquitin conjugating enzyme. SMG3 interacts with another grain size regulator, DGS1. Loss of function of SMG3 or DGS1 results in small grains, while overexpression of SMG3 or DGS1 leads to long grains. Further analyses showed that DGS1 is an active E3 ubiquitin ligase and colocates with SMG3 in the ER. SMG3 and DGS1 are involved in BR signaling. DGS1 ubiquitinates the BR receptor BRASSINOSTEROID INSENSITIVE 1 (BRI1) and affects its accumulation. Genetic analysis suggests that SMG3, DGS1, and BRI1 act together to regulate grain size and weight. In summary, our findings identify an ERAD-related E2-E3 pair that regulates grain size and weight, which gives insight into the function of ERAD in grain size control and BR signaling.

An SNW/SKI-INTERACTING PROTEIN influences endoreduplication and cell growth in Arabidopsis.

Endoreduplication plays an important role in cell growth and differentiation, but the mechanisms regulating endoreduplication are still elusive. We have previously reported that UBIQUITIN-SPECIFIC PROTEASE14 (UBP14) encoded by DA3 interacts with ULTRAVIOLETB INSENSITIVE4 (UVI4) to influence endoreduplication and cell growth in Arabidopsis (Arabidopsis thaliana). The da3-1 mutant possesses larger cotyledons and flowers with higher ploidy levels than the wild-type. Here, we identify the suppressor of da3-1 (SUPPRESSOR OF da3-1 3; SUD3), which encodes SNW/SKI-INTERACTING PROTEIN (SKIP). Biochemical studies demonstrate that SUD3 physically interacts with UBP14/DA3 and UVI4 in vivo and in vitro. Genetic analyses support that SUD3 acts in a common pathway with UBP14/DA3 and UVI4 to control endoreduplication. Our findings reveal an important genetic and molecular mechanism by which SKIP/SUD3 associates with UBP14/DA3 and UVI4 to modulate endoreduplication.