Send to

Choose Destination
J Biol Chem. 2015 Dec 4;290(49):29617-28. doi: 10.1074/jbc.M115.664649. Epub 2015 Oct 14.

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.

Author information

From the Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
the Proteome Exploration Laboratory, Beckman Institute, California Institute of Technology, Pasadena, California 91125, and.
the Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, United Kingdom.
the Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, Pennsylvania 19122.
From the Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029,


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 PLK1 (Polo-like kinase 1) 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 Polo box domain of PLK1 leading to phosphorylation of JLP at additional sites. Stable isotope labeling by amino acids in cell culture 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.


FOXK1; JLP; PLK1; mitosis; phosphorylation; protein-protein interaction; scaffold protein; serine/threonine protein kinase; transcription factor

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center