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Grb7 Protein Stability Modulated by Pin1 in Association with Cell Cycle Progression
Abstract
<div><p>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 <i>cis/trans</i> isomerase, Pin1. Our data show that phosphorylation of Grb7 protein on the Ser<sup>194</sup>-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 <i>cis/trans</i> 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.</p></div- Text
- Journal contribution
- Biophysics
- Biochemistry
- Medicine
- Microbiology
- Cell Biology
- Genetics
- Molecular Biology
- Immunology
- Developmental Biology
- Cancer
- Hematology
- Infectious Diseases
- Virology
- Computational Biology
- Biological Sciences not elsewhere classified
- Grb 7
- WW
- multi-domain adaptor protein
- Grb 7 protein
- regulation
- modulating Grb 7-mediated
- Grb 7 protein stability
- Grb 7 Protein Stability Modulated
- c-Jun N-terminal kinase
- G 2-M phase
- Cell Cycle Progression Growth factor receptor
- cell cycle progression