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

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

PloS one (2016-09-23)
Yu-Ling Tai, Li-Hsuan Tung, Yu-Chi Lin, Pei-Jung Lu, Pei-Yu Chu, Ming-Yang Wang, Wei-Pang Huang, Ko-Chien Chen, Hsinyu Lee, Tang-Long Shen
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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