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A means to an end: a role for phosphorylation in the degradation of Pax3
Author(s) -
Loupe Jacob M,
Miller Patrick J,
Iyengar Aditi S,
Hollenbach Andrew D
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.734.7
Subject(s) - phosphorylation , pax3 , transcription factor , microbiology and biotechnology , biology , tec , chemistry , gene , biochemistry , ionosphere , physics , astronomy
Pax3 is a transcription factor necessary for regulating the expression of genes crucial in early muscle development. Upon myogenic differentiation, Pax3 protein levels diminish due to increased proteasomal degradation. This degradation is signaled by Pax3 monoubiquitination by Taf1, a subunit of the TF II D general transcription complex. Our lab demonstrated that Pax3 is phosphorylated at only three sites present in the domain responsible for mediating protein‐protein interactions (Serines 201, 205, and 209). Unpublished data from this laboratory demonstrates that phosphorylation of Pax3 affects its ability to interact with known Pax3‐regulatory proteins, suggesting that phosphorylation is a potential mechanism to control Pax3 biological activity. Of the three identified sites, Ser201 is the only phosphorylation event present on Pax3 at the time of early differentiation when we begin to observe the degradation of Pax3. We show through immunofluorescence that as differentiation progresses, Pax3 phosphorylated at Ser201 localizes to the nucleolus, a known site of nuclear proteasomal degradation. Additionally, we perform in vitro interaction studies with GST‐Pax3 phosphomutants incubated with mouse primary myoblast total cell extract and show for the first time that phosphorylation at Ser201 promotes the ability of Pax3 to interact with Taf1 in differentiated myoblasts. (Funding: NCI R01 CA138656 )