JNK associated leucine zipper protein functions as a docking platform for Polo like kinase 1 and regulation of the associating transcription factor Forkhead box protein K1
Abstract
JLP (JNK associated Leucine zipper protein) is a scaffolding protein that interacts with various signaling proteins associated with coordinated regulation of cellular process such as endocytosis, motility, neurite outgrowth, cell proliferation and apoptosis. Here we identified Polo like kinase 1 (PLK1) as a novel interaction partner of JLP through mass spectrometric approaches. Our results indicate that JLP is phospho-primed by PLK1 on Thr 351, which is recognized by the PBD of PLK1 leading to phosphorylation of JLP at additional sites. SILAC and quantitative LC-MS/MS analysis was performed to identify PLK1 dependent JLP interacting proteins. Treatment of cells with the PLK1 kinase inhibitor BI2536 suppressed binding of the Forkhead box protein K1 (FOXK1) transcriptional repressor to JLP. JLP was found to interact with PLK1 and FOXK1 during mitosis. Moreover, knockdown of PLK1 affected the interaction between JLP and FOXK1. FOXK1 is a known transcriptional repressor of the CDK inhibitor p21/WAF1 and knockdown of JLP resulted in increased FOXK1 protein levels and a reduction of p21 transcript levels. Our results suggest a novel mechanism by which FOXK1 protein levels and activity are regulated by associating with JLP and PLK1.
Additional Information
© 2015 by The American Society for Biochemistry and Molecular Biology, Inc. First Published on October 14, 2015. EPR is supported by a grant from NIH RO1CA158209. AS is supported by a grant from the Wellcome Trust. The AM, MJS, SH is supported by the Gordon and Betty Moore Foundation through grant GBMF775 and the Beckman Institute. We thank Stacey J. Baker for critical reading of the manuscript.Attached Files
Published - J._Biol._Chem.-2015-Ramkumar-29617-28.pdf
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Additional details
- Alternative title
- JNK-associated leucine zipper protein functions as a docking platform for Polo-like kinase 1 and regulation of the associating transcription factor Forkhead box protein K1
- PMCID
- PMC4705960
- Eprint ID
- 61391
- Resolver ID
- CaltechAUTHORS:20151021-134113869
- Wellcome Trust
- GBMF775
- Gordon and Betty Moore Foundation
- Caltech Beckman Institute
- Created
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2015-10-22Created from EPrint's datestamp field
- Updated
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2022-05-19Created from EPrint's last_modified field