Grb7 protein stability modulated by pin1 in association with cell cycle progression
Journal
PLoS ONE
Journal Volume
11
Journal Issue
9
Pages
e0163617
Date Issued
2016
Author(s)
Tai, Y.-L., Tung, L.-H., Lin, Y.-C., Lu, P.-J., Chu, P.-Y., Wang, M.-Y., Huang, W.-P., Chen, K.-C., Lee, H., Shen, T.-L.
Tung L.-H.
Lin Y.-C.
Lu P.-J.
Chu P.-Y.
Wang M.-Y.
Huang W.-P.
Chen K.-C.
Lee H.
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.
SDGs
Type
journal article