WWP2 is required for normal cell cycle progression
Byeong Hyeok Choi1, Xun Che1, Changyan Chen2, Luo Lu3 and Wei Dai1
1 Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo Park, NY, USA
2 Center for Drug Discovery, Northeastern University, Boston, MA, USA
3 Division of Molecular Medicine, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Torrance, CA, USA
Correspondence:
Wei Dai, email:
Keywords: WWP2, Cell Cycle, Cyclin, Mitosis, Ubiquitin E3 ligase, Akt
Received: September 04, 2015 Accepted: October 01, 2015 Published: October 07, 2015
Abstract
WWP2 is a ubiquitin E3 ligase belonging to the Nedd4-like family. Given that WWP2 target proteins including PTEN that are crucial for regulating cell proliferation or suppressing tumorigenesis, we have asked whether WWP2 plays a role in controlling cell cycle progression. Here we report that WWP2 is necessary for normal cell cycle progression as its silencing significantly reduces the cell proliferation rate. We have identified that an isoform of WWP2 (WWP2-V4) is highly expressed in the M phase of the cell cycle. Silencing of WWP2 accelerates the turnover of cyclin E, which is accompanied by increased levels of phospho-histone H3 (p-H3) and cyclin B. Moreover, silencing of WWP2 results in compromised phosphorylation of AktS473, a residue whose phosphorylation is tightly associated with the activation of the kinase. Combined, these results strongly suggest that WWP2 is an important component in regulating the Akt signaling cascade, as well as cell cycle progression.
