C-TAK1 interacts with microphthalmia-associated transcription factor, Mitf, but not the related family member Tfe3.
Microphthalmia-associated transcription factor, Mitf, has been shown to be necessary for regulating genes involved in osteoclast differentiation. Previously it was shown by others that Mitf translocates from the cytoplasm to the nucleus upon M-CSF/RANKL signaling in osteoclasts. Mitf's movement is regulated by its interaction with 14-3-3 and the kinase C-TAK1. Here we demonstrate that the related family member, Tfe3, does not shuttle from the cytoplasm to the nucleus and does not interact with C-TAK1. We also demonstrate that overexpression of C-TAK1 inhibits the expression of Acp5 while a kinase dead C-TAK1 or a Mitf mutant that cannot interact with C-TAK1 increased expression of Acp5. Finally, we show that the catalytic subunit of protein phosphatase 2A is up-regulated in osteoclasts with M-CSF/RANKL signaling, indicating a possible mechanism for dephosphorylating Mitf on its 14-3-3 binding site and allowing Mitf to be translocated to the nucleus of osteoclasts.
Schwarz
Toni
T
Division of Orthodontics, Department of Developmental and Surgical Sciences, University of Minnesota School of Dentistry, 515 Delaware St. SE, Minneapolis, MN 55455, USA.
Murphy
Sharlene
S
Sohn
Chee
C
Mansky
Kim C
KC
D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000201:enzymology; D051379:Mice; D008822:Mice, Transgenic; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000201:enzymology; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D048948:14-3-3 Proteins; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; C068486:Tcfe3 protein, mouse; C111833:MARK3 protein, human; D017346:Protein Serine-Threonine Kinases; D054648:Protein Phosphatase 2