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

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-trans...

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Bibliographic Details
Published in:PloS one 2016-09, Vol.11 (9), p.e0163617-e0163617
Main Authors: Tai, Yu-Ling, Tung, Li-Hsuan, Lin, Yu-Chi, Lu, Pei-Jung, Chu, Pei-Yu, Wang, Ming-Yang, Huang, Wei-Pang, Chen, Ko-Chien, Lee, Hsinyu, Shen, Tang-Long
Format: Article
Language:English
Subjects:
Apoptosis
Biology and Life Sciences
Biotechnology
Breast cancer
c-Jun protein
Cell adhesion & migration
Cell cycle
Cell growth
Clinical medicine
Growth factors
Immunoglobulins
JNK protein
Kinases
Laboratories
Medical research
Molecular chains
Molecular modelling
Phosphorylation
Phosphotransferases
Physiology
Pin1 protein
Plant pathology
Post-translation
Proteasomes
Protein binding
Proteins
Proteolysis
Regulatory mechanisms (biology)
Research and Analysis Methods
Saccharomyces cerevisiae
Signal transduction
Signaling
Stability
Transcription factors
Tyrosine
Ubiquitin
Yeast
Zoology
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0163617