Oncotarget

Research Papers:

This article has been corrected. Correction in: Oncotarget. 2017; 8:39935.

p63α modulates c-Myc activity via direct interaction and regulation of MM1 protein stability

Anning Han _, Juan Li, Yimin Li, Yang Wang, Johann Bergholz, Yujun Zhang, Chenghua Li and Zhi-Xiong Xiao

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Oncotarget. 2016; 7:44277-44287. https://doi.org/10.18632/oncotarget.10187

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Abstract

Anning Han1, Juan Li1,*, Yimin Li1,*, Yang Wang1, Johann Bergholz1, Yujun Zhang1, Chenghua Li1, Zhi-Xiong Xiao1

1Center of Growth, Metabolism and Aging, Key Laboratory of Biological Resources and Ecological Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610064, China

*These authors have contributed equally to this work

Correspondence to:

Chenghua Li, email: lichenghua@scu.edu.cn

Zhi-Xiong Xiao, email: jimzx@scu.edu.cn

Keywords: p63, MM1, c-Myc, protein stability, cell cycle

Received: January 07, 2016     Accepted: May 16, 2016     Published: June 20, 2016

ABSTRACT

Both p53-related p63 and c-Myc are transcription factors playing key roles in cell proliferation, survival, development and tumorigenesis. In the present study, we identified that MM1, a c-Myc inhibitor, specifically binds to C-termini of p63α (including ΔNp63α and TAp63α). Further study demonstrates that p63α facilitates MM1 protein degradation via proteasomal pathway, resulting in elevation of c-Myc transactivation activity. Knockdown of ΔNp63α leads to decrease in c-Myc protein levels, concomitant with reduced expression of CDK4 and Cyclin D1, and impaired cell cycle progression, both of which are effectively reversed by simultaneous knockdown of MM1. Moreover, expression of p63 and CDK4 is concomitantly up-regulated in B-cell acute lymphoblastic leukemia. Together, this study reveals a novel crosstalk between p63 and c-Myc that may play an important role in cell cycle progression and tumorigenesis.


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