GLTSCR1 Negatively Regulates BRD4-Dependent Transcription Elongation and Inhibits CRC Metastasis.

ABSTRACT: Frameshift mutations frequently occur in colorectal cancer (CRC) with microsatellite instability (MSI), but the nature and biological function of many MSI-associated mutations remain elusive. Here, an MSI frameshift mutation is identified in glioma tumor suppressor candidate region gene 1 (GLTSCR1) that produces two C-terminal-truncated proteins. Additionally, GLTSCR1 is verified as a tumor suppressor that inhibits CRC metastasis. Through binding to bromodomains and the phosphorylation-dependent interaction domain of bromodomain protein 4 (BRD4) via the C-terminus, GLTSCR1 blocks oncogenic transcriptional elongation. However, truncated GLTSCR1 translocates into the cytoplasm and loses BRD4 binding domain, which induces the phosphorylation of RNA Pol II at Ser2 and dephosphory

SUBMITTER: Han F 

PROVIDER: S-EPMC6891902 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature