ASCC2

Last update 08 May 2025

Basic Info

Synonyms

activating signal cointegrator 1 complex subunit 2, ASC-1 complex subunit p100, ASC1p100

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Introduction

Ubiquitin-binding protein involved in DNA repair and rescue of stalled ribosomes (PubMed:29144457, PubMed:32099016, PubMed:32579943, PubMed:36302773). Plays a role in DNA damage repair as component of the ASCC complex (PubMed:29144457). Recruits ASCC3 and ALKBH3 to sites of DNA damage by binding to polyubiquitinated proteins that have 'Lys-63'-linked polyubiquitin chains (PubMed:29144457). Part of the ASC-1 complex that enhances NF-kappa-B, SRF and AP1 transactivation (PubMed:12077347). Involved in activation of the ribosome quality control (RQC) pathway, a pathway that degrades nascent peptide chains during problematic translation (PubMed:32099016, PubMed:32579943, PubMed:36302773). Specifically recognizes and binds RPS20/uS10 ubiquitinated by ZNF598, promoting recruitment of the RQT (ribosome quality control trigger) complex on stalled ribosomes, followed by disassembly of stalled ribosomes (PubMed:36302773).

100 Clinical Results associated with ASCC2

100 Translational Medicine associated with ASCC2

0 Patents (Medical) associated with ASCC2

Literatures (Medical) associated with ASCC2

01 Dec 2022·Molecular Case Studies

Whole-genome characterization of myoepithelial carcinomas of the soft tissue

Article

Author: Al Zoughbi, Wael ; Zhang, Tuo ; Mosquera, Juan Miguel ; Rubin, Brian P ; Rubin, Mark A ; Elemento, Olivier ; Imielinski, Marcin ; Cyrta, Joanna ; Motanagh, Samaneh ; Eng, Kenneth ; Wilkes, David C ; Sticca, Evan ; Rosiene, Joel ; Sboner, Andrea ; Mathew, Susan ; Kudman, Sarah ; Bareja, Rohan

Myoepithelial carcinomas (MECs) of soft tissue are rare and aggressive tumors affecting young adults and children, but their molecular landscape has not been comprehensively explored through genome sequencing. Here, we present the whole-exome sequencing (WES), whole-genome sequencing (WGS), and RNA sequencing findings of two MECs. Patients 1 and 2 (P1, P2), both male, were diagnosed at 27 and 37 yr of age, respectively, with shoulder (P1) and inguinal (P2) soft tissue tumors. Both patients developed metastatic disease, and P2 died of disease. P1 tumor showed a rhabdoid cytomorphology and a complete loss of INI1 (SMARCB1) expression, associated with a homozygousSMARCB1deletion. The tumor from P2 showed a clear cell/small cell morphology, retained INI1 expression and strong S100 positivity. By WES and WGS, tumors from both patients displayed low tumor mutation burdens, and no targetable alterations in cancer genes were detected. P2's tumor harbored anEWSR1::KLF15rearrangement, whereas the tumor from P1 showed a novelASCC2::GGNBP2fusion. WGS evidenced a complex genomic event involving mainly Chromosomes 17 and 22 in the tumor from P1, which was consistent with chromoplexy. These findings are consistent with previous reports ofEWSR1rearrangements (50% of cases) in MECs and provide a genetic basis for the loss of SMARCB1 protein expression observed through immunohistochemistry in 10% of 40% of MEC cases. The lack of additional driver mutations in these tumors supports the hypothesis that these alterations are the key molecular events in MEC evolution. Furthermore, the presence of complex structural variant patterns, invisible to WES, highlights the novel biological insights that can be gained through the application of WGS to rare cancers.

05 Apr 2022·Circulation

Identification of DNA Damage Repair Enzyme Ascc2 as Causal for Heart Failure With Preserved Ejection Fraction

Letter

Author: Pan, Calvin ; Jedian, Vida ; Zhou, Zhiqiang ; Guardino, Kristina ; Wang, Yu-Chen ; Cao, Yang ; Lusis, Aldons J. ; Campbell, Gillian ; Meng, Yonghong ; Wang, Jessica ; Li, Christopher

01 Feb 2022·Journal of Biological ChemistryQ2 · BIOLOGY

The ASCC2 CUE domain in the ALKBH3–ASCC DNA repair complex recognizes adjacent ubiquitins in K63-linked polyubiquitin

Q2 · BIOLOGY

Article

Author: Majumdar, Ananya ; Haile, Sara ; Osei-Asante, Emmanuella ; Baer, Julia G ; Anoh, Rita ; Veilleux, Julianna M ; Orland, Hannah A ; Schmelyun, Dhane P ; Ngandu, Christine K ; Mosammaparast, Nima ; Rodell, Rebecca ; Lombardi, Patrick M ; Syed, Shaheer H ; Kebreau, Kayla R ; Burke, Kate A ; Gray, Lauren N ; Rusanov, Timur ; Wolberger, Cynthia ; Hacker, Abigail R ; Shorb, Devin E

Alkylation of DNA and RNA is a potentially toxic lesion that can result in mutations and even cell death. In response to alkylation damage, K63-linked polyubiquitin chains are assembled that localize the Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3-Activating Signal Cointegrator 1 Complex Subunit (ASCC) repair complex to damage sites in the nucleus. The protein ASCC2, a subunit of the ASCC complex, selectively binds K63-linked polyubiquitin chains via its coupling of ubiquitin conjugation to ER degradation (CUE) domain. The basis for polyubiquitin-binding specificity was unclear, because CUE domains in other proteins typically bind a single ubiquitin and do not discriminate among different polyubiquitin linkage types. We report here that the ASCC2 CUE domain selectively binds K63-linked diubiquitin by contacting both the distal and proximal ubiquitin. The ASCC2 CUE domain binds the distal ubiquitin in a manner similar to that reported for other CUE domains bound to a single ubiquitin, whereas the contacts with the proximal ubiquitin are unique to ASCC2. Residues in the N-terminal portion of the ASCC2 α1 helix contribute to the binding interaction with the proximal ubiquitin of K63-linked diubiquitin. Mutation of residues within the N-terminal portion of the ASCC2 α1 helix decreases ASCC2 recruitment in response to DNA alkylation, supporting the functional significance of these interactions during the alkylation damage response. Our study reveals the versatility of CUE domains in ubiquitin recognition.

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ASCC2

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