| Literature DB >> 28877474 |
Xiao Ling Li1, Murugan Subramanian1, Matthew F Jones1, Ritu Chaudhary1, Deepak K Singh2, Xinying Zong2, Berkley Gryder3, Sivasish Sindri3, Min Mo4, Aaron Schetter5, Xinyu Wen3, Swetha Parvathaneni6, Dickran Kazandjian5, Lisa M Jenkins7, Wei Tang8, Fathi Elloumi9, Jennifer L Martindale10, Maite Huarte11, Yuelin Zhu12, Ana I Robles5, Susan M Frier13, Frank Rigo13, Maggie Cam9, Stefan Ambs8, Sudha Sharma6, Curtis C Harris5, Mary Dasso4, Kannanganattu V Prasanth2, Ashish Lal14.
Abstract
Basal p53 levels are tightly suppressed under normal conditions. Disrupting this regulation results in elevated p53 levels to induce cell cycle arrest, apoptosis, and tumor suppression. Here, we report the suppression of basal p53 levels by a nuclear, p53-regulated long noncoding RNA that we termed PURPL (p53 upregulated regulator of p53 levels). Targeted depletion of PURPL in colorectal cancer cells results in elevated basal p53 levels and induces growth defects in cell culture and in mouse xenografts. PURPL associates with MYBBP1A, a protein that binds to and stabilizes p53, and inhibits the formation of the p53-MYBBP1A complex. In the absence of PURPL, MYBBP1A interacts with and stabilizes p53. Silencing MYBBP1A significantly rescues basal p53 levels and proliferation in PURPL-deficient cells, suggesting that MYBBP1A mediates the effect of PURPL in regulating p53. These results reveal a p53-PURPL auto-regulatory feedback loop and demonstrate a role for PURPL in maintaining basal p53 levels. Published by Elsevier Inc.Entities:
Keywords: CRC; HuR; LINC01021; LOC643401; MYBBP1A; PURPL; RP11-46C20.1; lincRNA; lncRNA; p53
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Year: 2017 PMID： 28877474 PMCID： PMC5777516 DOI： 10.1016/j.celrep.2017.08.041
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423