NRIP/DCAF6 stabilizes the androgen receptor protein by displacing DDB2 from the CUL4A-DDB1 E3 ligase complex in prostate cancer
Journal
Oncotarget
Journal Volume
8
Journal Issue
13
Pages
21501
Date Issued
2017-03-28
Author(s)
Abstract
Both nuclear receptor interaction protein (NRIP) and DNA damage binding protein 2 (DDB2) belong to the Cullin 4 (CUL4)-DDB1 binding protein family and are androgen receptor (AR)-interacting proteins. Here, we investigated the expression patterns of the NRIP, DDB2 and AR proteins in human prostate cancer tissues and found that the expression levels of NRIP and AR were higher, but the DDB2 level was lower, in prostate cancer tissues than in non-neoplastic controls, suggesting NRIP as a candidate tumor promoter and DDB2 as a tumor suppressor in prostate cancer. Furthermore, both NRIP and DDB2 shared the same AR binding domain; they were competitors for the AR, but not for DDB1 binding, in the AR-DDB2-DDB1-CUL4A complex. Conclusively, NRIP stabilizes the AR protein by displacing DDB2 from the AR-DDB2 complex. Consistent with our hypothesis, a specific expression pattern with high levels of NRIP and AR, together with a low level of DDB2, was found more frequently in the human prostate cancer tissues with a cribriform pattern than in non-cribriform tumors, suggesting that disruption of the balance between NRIP and DDB2 may change AR protein homeostasis and contribute to pathogenesis in certain aggressive types of prostate cancer.
Subjects
AR; Cul4-DDB1; DDB2; NRIP/DCAF6; cribriform prostate cancer
SDGs
Other Subjects
androgen receptor; cullin 4 DNA damage binding protein 1; DNA damage binding protein 2; nuclear receptor interaction protein; oncoprotein; unclassified drug; Article; binding affinity; cancer grading; cancer growth; cancer tissue; controlled study; down regulation; human; human cell; human tissue; pathogenesis; prostate cancer; protein binding; protein degradation; protein expression; protein function; protein localization; protein protein interaction; protein stability; ubiquitination; upregulation
Publisher
IMPACT JOURNALS LLC
Type
journal article