Ask about this productRelated genes to: UIMC1 antibody
- Gene:
- UIMC1 NIH gene
- Name:
- ubiquitin interaction motif containing 1
- Previous symbol:
- -
- Synonyms:
- RAP80
- Chromosome:
- 5q35.2
- Locus Type:
- gene with protein product
- Date approved:
- 2006-10-27
- Date modifiied:
- 2014-11-19
Related products to: UIMC1 antibody
Related articles to: UIMC1 antibody
- Growing evidence has identified potential biomarkers of cognitive-behavioural therapy (CBT) efficacy in obsessive-compulsive disorder (OCD). Genetic and epigenetic mechanisms (e.g., polymorphisms, DNA methylation) contribute to OCD pathogenesis and CBT response variability, establishing them as a key research focus. To evaluate their associations with CBT outcomes in OCD, we conducted a systematic review of PubMed, Web of Science, CNKI, and Cochrane Library (from inception to January 2025), identifying eight studies that met rigorous inclusion criteria. The identified predictors included: (1) Genetic polymorphisms (BDNF); (2) Epigenetic modifications (DNA methylation of MAOA, SLC6A4, OXTR, PIWIL1, MIR886, PLEKHA1, KCNQ1, TRPM8, HEBP1, HTR7P1, MAPK8IP3, ENAH, RABGGTB (SNORD45C), MYEF2, GALK2, CEP192, and UIMC1). These markers may influence neural plasticity, neurotransmitter regulation, and related processes, providing molecular substrates for the observed treatment effects. Converging evidence suggests that distinct neurocognitive mechanisms may mediate CBT efficacy in OCD, particularly fear extinction learning and goal-directed behaviors (GDBs), which we analyze mechanistically. Future studies should integrate polygenic risk scores (PRS) with functional neuroimaging to dissect individual variability in CBT response, mainly through cortico-striato-thalamo-cortical (CSTC) circuit profiling. To our knowledge, this is the first systematic review synthesizing genetic and epigenetic predictors of CBT response in OCD; these findings provide compelling evidence for biomarkers for CBT personalization in OCD, advancing a novel precision psychiatry framework. - Source: PubMed
Publication date: 2025/05/03
Chen YuWang PengchongLi Zhanjiang - In selective macroautophagy/autophagy, cargo recruitment is mediated by MAP1LC3/LC3-interacting regions (LIRs)/Atg8-family interacting motifs (AIMs) in the cargo or cargo receptor proteins. The binding of these motifs to LC3/Atg8 proteins at the phagophore membrane is often modulated by post-translational modifications, especially phosphorylation. As a challenge for computational LIR predictions, sequences may contain the short canonical (W/F/Y)XX(L/I/V) motif without being functional. Conversely, LIRs may be formed by non-canonical but functional sequence motifs. AlphaFold2 has proven to be useful for LIR predictions, even if some LIRs are missed and proteins with thousands of residues reach the limits of computational feasibility. We present a fragment-based approach to address these limitations. We find that fragment length and phosphomimetic mutations modulate the interactions predicted by AlphaFold2. Systematic fragment screening for a range of target proteins yields structural models for interactions that AlphaFold2 and AlphaFold3 fail to predict for full-length targets. We provide guidance on fragment choice, sequence tuning, LC3 isoform effects, and scoring for optimal LIR screens. Finally, we also test the transferability of this general framework to SUMO-SIM interactions, another type of protein-protein interaction involving short linear motifs (SLiMs).: 2-HP-LIR: ncLIR binding either or both HPs with non-canonical residues; AIM: Atg8-family interacting motif; ap. LIR: antiparallel LIR; .; ; AT5G06830/C53 (.): CDK5RAP3-like protein; Atg8/ATG8: autophagy related 8, in yeast and plants, respectively; ATG8CL: ATG8C-like of (potato); ATG8E: ATG8e of .; Av. num. of contacts: average number of heavy atom contacts; BCL2: BCL2 apoptosis regulator; BNIP3: BCL2 interacting protein 3; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CALR: calreticulin; can. LIR: canonical LIR; CDF: cumulative distribution function; CDK5RAP3/C53 (.): CDK5 regulatory subunit associated protein 3; [DE]W[DE]-LIR: TRIM5-like ncLIR; DSK2A: ubiquitin domain-containing protein DSK2a; FUNDC1: FUN14 domain containing 1; GABARAP: GABA type A receptor-associated protein; HP0/1/2: hydrophobic pocket 0/1/2; HP0-LIR: ncLIR engaging HP0; .; ; lcLIR: low-confidence LIR (ncLIR not similar to previously characterized ncLIRs); LDS: LIR-docking site; LIR: LC3-interacting region; LO score: length-weighted fraction of occurrence score; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MD: molecular dynamics; MEFV/pyrin: MEFV innate immunity regulator, pyrin; minPAE: minimum PAE; MSA: multiple sequence alignment; ncLIR: non-canonical LIR; NPC: nuclear pore complex; Nup159: nucleoporin 159; NUP214: nucleoporin 214; OPTN: optineurin; other@LDS: other interaction proximal to the LIR-docking site; PAE: predicted aligned error; PDCD6IP: programmed cell death 6 interacting protein; PDF: probability distribution function; pLDDT: predicted local-distance difference test; PLEKHM1: pleckstrin homology and RUN domain containing M1; PTM: post-translational modification; sAIM: shuffled AIM (ncLIR with shuffled motif); seq.: sequence; SIM: SUMO-interacting motif; SLiM: short linear motif; SMN1/SMN: survival of motor neuron 1, telomeric; ST: phosphomimetic; STBD1: starch binding domain 1; STK3: serine/threonine kinase 3; SUMO: small ubiquitin like modifier; TBC1D2/TBC1D2A: TBC1 domain family member 2; TEX264: testis expressed 264, ER-phagy receptor; TRIM5/TRIM5α: tripartite motif-containing protein 5; UDS: UIM-docking site; UIM: ubiquitin-interacting motif; UIMC1/RAP80: ubiquitin interaction motif containing 1; ULK1: unc-51 like autophagy activating kinase 1; ULK2: unc-51 like autophagy activating kinase 2; WT: wild type. - Source: PubMed
Publication date: 2025/05/04
Stuke Jan Felix MaximilianHummer Gerhard - PARP inhibitor (PARPi) resistance presents a significant challenge in ovarian cancer treatment, necessitating the development of effective therapeutic strategies to overcome this resistance and improve patient outcomes. Our study demonstrated that elevated expression of SRY-box 9 (SOX9) contributes to olaparib resistance in ovarian cancer. Mechanistically, the deubiquitinating enzyme USP28 was identified as a novel interacting partner of SOX9. USP28 inhibited the ubiquitination and subsequent degradation of SOX9, which is mediated by the E3 ubiquitin ligase FBXW7 during olaparib treatment. ChIP-Seq analysis revealed that SOX9 binds to the promoters of key DNA damage repair (DDR) genes (SMARCA4, UIMC1, and SLX4), thereby regulating DDR processes in ovarian cancer. Additionally, USP28 promoted olaparib resistance by stabilizing SOX9 protein and enhancing DNA damage repair. Furthermore, the USP28 specific inhibitor AZ1 reduced SOX9 protein stability and increased the sensitivity of ovarian cancer cells to olaparib. In conclusion, targeted inhibition of USP28 promoted ubiquitination-mediated degradation of SOX9, thereby impairing DNA damage repair capabilities and sensitizing ovarian cancer cells to PARPi. These findings elucidate the underlying mechanisms of PARPi resistance in ovarian cancer and suggest the potential efficacy of combining USP28 inhibitors with PARPi to overcome this resistance. - Source: PubMed
Publication date: 2025/04/16
Han FangQi GonghuaLi RongrongPeng JialiYan ShiYuan CunzhongKong BeihuaMa Hanlin - Chronic liver disease is becoming a leading cause of illness and mortality in patients living with human immunodeficiency virus (HIV; PLWH) undergoing suppressive anti-retroviral therapy. Its primary etiology is coinfection with hepatitis B and C virus (HBV and HCV, respectively). Chronic liver inflammation and fibrosis can potentially lead to the development of hepatocellular carcinoma (HCC). Therefore, monitoring of the disease progression in PLWH is required. The present study aimed to explore plasma protein profiles of PLWH and those coinfected with HBV and HCV using shotgun proteomics. HIV-monoinfected, HIV/HBV-coinfected, HIV/HCV-coinfected and uninfected control individuals were recruited. Patients in the three virus-infected groups had significantly higher levels of liver fibrosis indices (fibrosis-4 score and aspartate aminotransferase to platelet ratio index) compared with the control group. Liquid chromatography-tandem mass spectrometry analysis of plasma samples identified 1,074 proteins that were differentially expressed, where subsequent partial least squares-discriminant analysis model demonstrated clear clustering of proteomes from the four sample groups; 18 proteins that were significantly differentially expressed. Heatmap analysis identified two main groups of proteins, six proteins being upregulated only in the HIV/HBV-coinfection group and 10 proteins downregulated in all three virally infected groups. STITCH 5.0 analysis predicted an interaction network containing two identified proteins in the latter group, specifically ubiquitin interaction motif-containing 1 (UIMC1) and haptoglobin (HP), which are part of the profibrogenic TGF-1β/SMAD, inflammatory TNF and tumor suppressor BRCA1 pathways. Expression levels of UIMC1 and HP were significantly lower in HIV-infected groups compared with those in uninfected controls. Altogether, these proteomics data provide protein expression profiles potentially associated with HIV infection and coinfection with HBV/HCV, which may be applied to predict progression to advanced liver disease or HCC in PLWH. - Source: PubMed
Publication date: 2024/08/26
Tarnathummanan ChewapornSoimanee ThanawanKhattiya JanyaSretapunya WarisaraPhaonakrop NarumonRoytrakul SittirukAkekawatchai Chareeporn - Breast Cancer Type 1 Susceptibility Protein (BRCA1) is a tumor-suppressor protein that regulates various cellular pathways, including those that are essential for preserving genome stability. One essential mechanism involves a BRCA1-A complex that is recruited to double-strand breaks (DSBs) by RAP80 before initiating DNA damage repair (DDR). How RAP80 itself is recruited to DNA damage sites, however, is unclear. Here, we demonstrate an intrinsic correlation between a methyltransferase DOT1L-mediated RAP80 methylation and BRCA1-A complex chromatin recruitment that occurs during cancer cell radiotherapy resistance. Mechanistically, DOT1L is quickly recruited onto chromatin and methylates RAP80 at multiple lysines in response to DNA damage. Methylated RAP80 is then indispensable for binding to ubiquitinated H2A and subsequently triggering BRCA1-A complex recruitment onto DSBs. Importantly, DOT1L-catalyzed RAP80 methylation and recruitment of BRCA1 have clinical relevance, as inhibition of DOT1L or RAP80 methylation seems to enhance the radiosensitivity of cancer cells both in vivo and in vitro. These data reveal a crucial role for DOT1L in DDR through initiating recruitment of RAP80 and BRCA1 onto chromatin and underscore a therapeutic strategy based on targeting DOT1L to overcome tumor radiotherapy resistance. - Source: PubMed
Publication date: 2024/08/22
Tang HuangqiLu Ya-FeiZeng RongshengLiu ChaohuaShu YuxinWu YupeiSu JiajieDi LongjiangQian JinqinZhang JunTian YuanLu XiaopengPei Xin-HaiZhu QianZhu Wei-Guo