Premium
Analysis of Pax3 phosphorylation in regulating DNA binding in early myogenic differentiation
Author(s) -
Hollenbach Andrew D,
Loupe Jacob M,
Iyengar Aditi S,
Miller Patrick J
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.734.8
Subject(s) - phosphorylation , pax3 , transcription factor , microbiology and biotechnology , biology , myogenesis , cell cycle , gene , genetics , myocyte
Pax3, a member of the paired‐class homeodomain family of transcription factors, is essential for regulating early myogenic differentiation. In undifferentiated cells it regulates the expression of genes that promote proliferation while simultaneously inhibiting differentiation. Upon receiving signals to differentiate, Pax3 then promotes the expression of downstream myogenic factors. Literature evidence suggests that phosphorylation of Pax3 contributes to its biological activities. Consistent with this fact we have identified three sites of phosphorylation on Pax3 (Serines 201, 205, and 209). In the present work we examine the effects of phosphorylation on the ability of Pax3 to bind to DNA and activate transcription. We demonstrate that phosphorylation of Pax3 at specific sites inhibits the ability of Pax3 to bind to DNA in vitro and alters its ability to interact with the co‐repressor hDaxx. Further, we provide evidence to suggest that the decision to enter differentiation occurs in the G1 phase of the cell cycle, for which we initiated studies to examine cell cycle‐dependent changes of Pax3 phosphorylation. Taken together, these results allow us to propose a working model to describe how phosphorylation regulates Pax3 biological activity in early myogenesis. (Funding: NCI R01 CA138656)