title: Grb7 Protein Stability Modulated by Pin1 in Association with Cell Cycle Progression.
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.
authors.affiliation: Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, Taiwan.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Tai
authors.affiliation: Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, Taiwan.
authors.forename: Li-Hsuan
authors.initials: LH
authors.lastname: Tung
authors.affiliation: Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, Taiwan.
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Institute of Clinical Medicine, Medical College, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Pei-Jung
authors.initials: PJ
authors.lastname: Lu
authors.affiliation: Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, Taiwan.|Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, Connecticut, United States of America.
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Chu
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Wang
authors.affiliation: Institute of Zoology, National Taiwan University, Taipei, Taiwan.
authors.forename: Wei-Pang
authors.initials: WP
authors.lastname: Huang
authors.affiliation: Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, Taiwan.
authors.forename: Ko-Chien
authors.initials: KC
authors.lastname: Chen
authors.affiliation: Institute of Zoology, National Taiwan University, Taipei, Taiwan.|Center for Biotechnology, National Taiwan University, Taipei, Taiwan.
authors.forename: Hsinyu
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, Taiwan.|Center for Biotechnology, National Taiwan University, Taipei, Taiwan.
authors.forename: Tang-Long
authors.initials: TL
authors.lastname: Shen