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

Publication date: 5 September 2017
Source:Cell Reports, Volume 20, Issue 10
Author(s): Xiao Ling Li, Murugan Subramanian, Matthew F. Jones, Ritu Chaudhary, Deepak K. Singh, Xinying Zong, Berkley Gryder, Sivasish Sindri, Min Mo, Aaron Schetter, Xinyu Wen, Swetha Parvathaneni, Dickran Kazandjian, Lisa M. Jenkins, Wei Tang, Fathi Elloumi, Jennifer L. Martindale, Maite Huarte, Yuelin Zhu, Ana I. Robles, Susan M. Frier, Frank Rigo, Maggie Cam, Stefan Ambs, Sudha Sharma, Curtis C. Harris, Mary Dasso, Kannanganattu V. Prasanth, Ashish Lal
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.

Graphical abstract

Teaser

For a cell to divide, the tumor suppressor protein p53 must be kept at low levels. Li et al. find that a long noncoding RNA PURPL allows cancer cells to divide by keeping p53 levels low. PURPL binds to the p53 regulator MYBBP1A to suppress p53 levels and facilitate cell proliferation.


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