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

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

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


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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