Loading...
CRL4-DCAF8L1 Regulates BRCA1 and BARD1 Protein Stability
Liu, Fei Han, Qianying Zhang, Ting Chang, Fen Deng, Jingcheng Huang, Xiaotian Wang, Weiping Xu, Yongjie Li, Qin Xu, Luzheng
Liu, Fei
Han, Qianying
Zhang, Ting
Chang, Fen
Deng, Jingcheng
Huang, Xiaotian
Wang, Weiping
Xu, Yongjie
Li, Qin
Xu, Luzheng
Citations
Altmetric:
Genre
Journal article
Date
2022-01-24
Advisor
Committee member
Department
Permanent link to this record
Collections
Research Projects
Organizational Units
Journal Issue
DOI
http://dx.doi.org/10.7150/ijbs.57178
Abstract
BRCA1 is frequently down-regulated in breast cancer, the underlying mechanism is unclear. Here we identified DCAF8L1, an X-linked gene product, as a DDB1-Cullin associated Factor (DCAF) for CUL4 E3 ligases to target BRCA1 and BARD1 for proteasomal degradation. Forced expression of DCAF8L1 caused reduction of BRCA1 and BARD1, and impaired DNA damage repair function, conferring increased sensitivity to irradiation and DNA damaging agents, as well as Olaparib, a PARPi anticancer drug; while depletion of DCAF8L1 restored BRCA1 and suppressed the growth of its xenograft tumors. Furthermore, the expression of DCAF8L1 was induced in human H9 ES cells during transition from primed to naïve state when Xi chromosome was reactivated. Aberrant expression of DCAF8L1 was observed in human breast fibroadenoma and breast cancer. These findings suggest that CRL4DCAF8L1 is an important E3 ligase that may participate in the development of breast cancer, probably through regulating the stability of BRCA1 and BARD1 tumor suppressor, linking BRCA1 and X chromosome inactivation to breast carcinogenesis.
Description
Citation
Liu F, Han Q, Zhang T, Chang F, Deng J, Huang X, Wang W, Xu Y, Li Q, Xu L, Zhang B, Li W, Li L, Su Y, Li Y, Shao G. CRL4-DCAF8L1 Regulates BRCA1 and BARD1 Protein Stability. Int J Biol Sci 2022; 18(4):1434-1450. doi:10.7150/ijbs.57178. https://www.ijbs.com/v18p1434.htm
Citation to related work
Ivyspring International Publisher
Has part
International Journal of Biological Sciences, Vol. 18
ADA compliance
For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu