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
- Deubiquitylases modulate cellular processes by removing monoubiquitin or cleaving polyubiquitin chains. The ARISC-RAP80 complex partners with BRCA1-BARD1 to form the BRCA1-A supercomplex, which recognises K63-linked ubiquitin chains at DNA damage sites. ARISC-RAP80 contains multiple ubiquitin-binding sites, yet how these influence recognition and cleavage of K63-polyubiquitylated substrates remains unknown. We discover that a composite three-subunit interface allows ARISC-RAP80 to position K63-linked polyubiquitin chains in its catalytic site. Substrate recognition is further supported by RAP80 and non-catalytic ubiquitin-binding sites that impose a compact conformation on K63-polyubiquitylated substrates. This mechanism exploits the inherent flexibility of long ubiquitin chains and differs considerably from other deubiquitylases. Structure-guided mutageneses validate ubiquitin chain interactions, and cell-based assays demonstrate a functional role of the observed interfaces in chromatin recruitment. Our findings define mechanisms of polyubiquitin chain decoding and cleavage by ARISC-RAP80, linking ubiquitin reading and erasing functions to BRCA1-A mediated DNA damage responses. - Source: PubMed
Publication date: 2026/08/11
Foglizzo MartinaDatta ArindamDegtjarik OksanaPerera HirunikaLiburd JordanSykora Upasana MGanji Sri RanjaniWildsmith GemmaChandler FrancescaCampbell Lisa JCalabrese Antonio NGreenberg Roger AZeqiraj Elton - In response to DNA double-strand breaks (DSBs), 5'-3' resection is required for production of single-stranded DNA (ssDNA) and commitent of homologous recombination (HR). Here, we demonstrated that CDW19S, a DSB-bound 19S proteasome variant, coordinates phasic control of long-range resection in a spatial-separated manner. Phase I exploits a panel of ubiquitin modifications on RAP80 (6Kub) as a hesitation mechanism to restrain BRCA1 loading. The deubiquitinase POH1, an integral component of CDW19S, removes 6Kub to allow BRCA1 assembly with BRCA1-A complex and firing of extensive resection. Following the action of phase I apparatus that is metazoan-specific, evolutionarily conserved phase II takes the relay in more distal compartments by imposing CDW19S-engaged CRL4WDR70 E3 ligase to degrade ADRM1, leading to the full-range ssDNA production dedicated for HR activation. The phasic regulation stimulates the repositioning of 53BP1-dependent resection barriers: 6Kub removal and BRCA1 loading overcome the 53BP1/PTIP barrier in phase I, and the demolition of ADRM1 antagonizes 53BP1/RIF1. Importantly, the phasic control of extensive resection serves for the tight control of ssDNA production, securing HR activation and preventing toxic repair mechanisms. Aggregately, our work reveals a coordinative function of CDW19S facilitating sufficient end resection that is crucial for error-free DNA repair. - Source: PubMed
Zeng MingTang ZizhiLi ChunyiRen LaifengWang XiaojunCarr AntonyLiu Cong - 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