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Altered states of Pax3 phosphorylation contribute to regulation in melanocytes and melanoma
Author(s) -
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.734.6
Subject(s) - phosphorylation , melanoma , pax3 , skin cancer , cancer research , biology , microbiology and biotechnology , transcription factor , melanocyte , cancer , genetics , gene
Melanoma is the deadliest form of skin cancer with an alarming increase in incidence, dismal prognosis and resistance to chemotherapy. Thus, a better understanding of the mechanisms controlling the aberrant expression of melanoma factors will assist in developing urgently needed alternative approaches to melanoma treatment. One potential target is the developmentally crucial transcription factor Pax3, which is up‐regulated by 2500 fold in melanoma. Our lab has shown that in mouse myoblasts Pax3 is phosphorylated at three serines (Serines 201, 205 and 209) in a region that mediates protein‐protein interactions. Additionally, Pax3 phosphorylation patterns vary during the course of differentiation with phosphorylation of Ser205 occurring only in proliferating cells. In this study, we demonstrate for the first time that Pax3 is phosphorylated in melanocytes as well as in melanoma cells. In contrast to melanocytes, Pax3 is almost exclusively phosphorylated at Ser205 in melanoma cells, an event that is exclusive to proliferating cells. Also, we show that phosphorylation of Pax3 enables its interaction with factors Lef1 and SOX10. Our results suggest that Pax3 phosphorylation regulates the expression of downstream targets by altering its ability to interact with co‐regulatory proteins and an aberrant change in Pax3 phosphorylation contributes to the development of melanoma. (Funding: NCI R01 CA138656 )