Identification of XBP1-u as a novel regulator of the MDM2/p53 axis using an shRNA library.

ABSTRACT: Cell cycle progression is a tightly controlled fundamental process in living cells, with any defects being closely linked to various abnormalities. The tumor suppressor p53/p21 axis is a core pathway controlling cell cycle progression; however, its regulatory mechanism has not been fully elucidated. In an effort to unravel this crucial network, we screened a short hairpin RNA expression vector library and identified unspliced X-box binding protein 1 (XBP1-u) as a novel and critical regulator of the p53/p21 axis. Specifically, XBP1-u negatively regulates the p53/p21 axis by enhancing p53 ubiquitination, which in turn down-regulates p21 expression. We show that XBP1-u suppression induces G0-G1 phase arrest and represses cell proliferation. We further report that the carboxyl terminus of XBP1

SUBMITTER: Huang C 

PROVIDER: S-EPMC5647124 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature