title: WWP2 is required for normal cell cycle progression.
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 Akt(S473), 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.
authors.affiliation: Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo Park, NY, USA.
authors.forename: Byeong Hyeok
authors.initials: BH
authors.lastname: Choi
authors.affiliation: Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo Park, NY, USA.
authors.forename: Xun
authors.initials: X
authors.lastname: Che
authors.affiliation: Center for Drug Discovery, Northeastern University, Boston, MA, USA.
authors.forename: Changyan
authors.initials: C
authors.lastname: Chen
authors.affiliation: Division of Molecular Medicine, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Torrance, CA, USA.
authors.forename: Luo
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo Park, NY, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Dai
keywords: Akt; Cell Cycle; Cyclin; Mitosis; Ubiquitin E3 ligase; WWP2