Phosphorylation-dependent binding of human transcription factor MOK2 to lamin A/C.
Human MOK2 is a DNA-binding transcriptional repressor. Previously, we identified nuclear lamin A/C proteins as protein partners of hsMOK2. Furthermore, we found that a fraction of hsMOK2 protein was associated with the nuclear matrix. We therefore suggested that hsMOK2 interactions with lamin A/C and the nuclear matrix may be important for its ability to repress transcription. In this study, we identify JNK-associated leucine zipper and JSAP1 scaffold proteins, two members of c-Jun N-terminal kinase (JNK)-interacting proteins family as partners of hsMOK2. Because these results suggested that hsMOK2 could be phosphorylated, we investigated the phosphorylation status of hsMOK2. We identified Ser38 and Ser129 of hsMOK2 as phosphorylation sites of JNK3 kinase, and Ser46 as a phosphorylation site of Aurora A and protein kinase A. These three serine residues are located in the lamin A/C-binding domain. Interestingly, we were able to demonstrate that the phosphorylation of hsMOK2 interfered with its ability to bind lamin A/C.
Harper
Maryannick
M
CNRS-FRE2937, Institut André Lwoff, Villejuif, France.
Tillit
Jeanne
J
Kress
Michel
M
Ernoult-Lange
Michèle
M
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D064127:Aurora Kinases; D001665:Binding Sites; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D024202:Electrophoretic Mobility Shift Assay; D006367:HeLa Cells; D006801:Humans; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D048057:Mitogen-Activated Protein Kinase 10 / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D016335:Zinc Fingers
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D034904:Lamin Type A; D011993:Recombinant Fusion Proteins; C111047:SPAG9 protein, human; C484253:ZNF239 protein, human; C440308:lamin C; D010768:Phosphoserine; D012694:Serine; D048057:Mitogen-Activated Protein Kinase 10; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases