3 years ago

Long Noncoding RNA PURPL Suppresses Basal p53 Levels and Promotes Tumorigenicity in Colorectal Cancer

Long Noncoding RNA PURPL Suppresses Basal p53 Levels and Promotes Tumorigenicity in Colorectal Cancer
Ashish Lal, Stefan Ambs, Maite Huarte, Matthew F. Jones, Kannanganattu V. Prasanth, Fathi Elloumi, Susan M. Frier, Lisa M. Jenkins, Berkley Gryder, Maggie Cam, Xinying Zong, Min Mo, Ana I. Robles, Yuelin Zhu, Jennifer L. Martindale, Wei Tang, Sivasish Sindri, Murugan Subramanian, Curtis C. Harris, Ritu Chaudhary, Sudha Sharma, Xinyu Wen, Xiao Ling Li, Mary Dasso, Dickran Kazandjian, Deepak K. Singh, Frank Rigo, Swetha Parvathaneni, Aaron Schetter

Summary

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.

Publisher URL: http://www.cell.com/cell-reports/fulltext/S2211-1247(17)31148-8

DOI: 10.1016/j.celrep.2017.08.041

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