Abstract
Abraxas brother 1 (ABRO1) has been reported to be a component of the BRISC complex, a multiprotein complex that specifically cleaves ‘Lys-63’-linked ubiquitin. However, current knowledge of the functions of ABRO1 is limited. Here we report that ABRO1 is frequently downregulated in human liver, kidney, breast and thyroid gland tumour tissues. Depletion of ABRO1 in cancer cells reduces p53 levels and enhances clone formation and cellular transformation. Conversely, overexpression of ABRO1 suppresses cell proliferation and tumour formation in a p53-dependent manner. We further show that ABRO1 stabilizes p53 by facilitating the interaction of p53 with USP7. DNA-damage induced accumulation of endogenous ABRO1 as well as translocation of ABRO1 to the nucleus, and the induction of p53 by DNA damage is almost completely attenuated by ABRO1 depletion. Our study shows that ABRO1 is a novel p53 regulator that plays an important role in tumour suppression and the DNA damage response.
Highlights
Abraxas brother 1 (ABRO1) has been reported to be a component of the BRISC complex, a multiprotein complex that cleaves ‘Lys-63’-linked ubiquitin
ABRO1 is homologous to CCDC98/Abraxas, sharing 39% sequence homology within the amino-terminal region, which contains a structural domain that interacts with subunits NBA1, BRE and BRCC36
We report that ABRO1 controls the deubiquitinating enzymes (DUBs) activity of USP7 on p53 and demonstrate that ABRO1 plays a role in tumorigenesis and in the DNA damage response
Summary
Abraxas brother 1 (ABRO1) has been reported to be a component of the BRISC complex, a multiprotein complex that cleaves ‘Lys-63’-linked ubiquitin. Our study shows that ABRO1 is a novel p53 regulator that plays an important role in tumour suppression and the DNA damage response. Recent studies have revealed that ABRO1 is part of the BRISC complex (BRCC36-containing isopeptidase complex), a multi-protein complex that cleaves Lys-63-linked ubiquitin[41,42,43,44]. This complex, which uses ABRO1 instead of Abraxas and does not contain RAP80, appears to represent a major K63-Ub-directed DUB activity in the cytoplasm[41,45].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
