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PLoS One. 2016 Sep 22;11(9):e0163617. doi: 10.1371/journal.pone.0163617.

Grb7 Protein Stability Modulated by Pin1 in Association with Cell Cycle Progression.

Author information

1
Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, Taiwan.
2
Institute of Clinical Medicine, Medical College, National Cheng Kung University, Tainan, Taiwan.
3
Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, Connecticut, United States of America.
4
Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
5
Institute of Zoology, National Taiwan University, Taipei, Taiwan.
6
Center for Biotechnology, National Taiwan University, Taipei, Taiwan.

Abstract

Growth factor receptor bound protein-7 (Grb7) is a multi-domain adaptor protein that is co-opted by numerous tyrosine kinases involved in various cellular signaling and functions. The molecular mechanisms underlying the regulation of Grb7 remain unclear. Here, we revealed a novel negative post-translational regulation of Grb7 by the peptidyl-prolyl cis/trans isomerase, Pin1. Our data show that phosphorylation of Grb7 protein on the Ser194-Pro motif by c-Jun N-terminal kinase facilitates its binding with the WW domain of Pin1. Subsequently, Grb7 is degraded by the ubiquitin- and proteasome-dependent proteolytic pathway. Indeed, we found that Pin1 exerts its peptidyl-prolyl cis/trans isomerase activity in the modulation of Grb7 protein stability in regulation of cell cycle progression at the G2-M phase. This study illustrates a novel regulatory mechanism in modulating Grb7-mediated signaling, which may take part in pathophysiological consequences.

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