TGF-beta targets PAX3 to control melanocyte differentiation.
In the absence of UV radiation, keratinocytes secrete TGF-beta which blocks melanocyte differentiation. Yang et al. (2008), in a recent issue of Molecular Cell, show that TGF-beta induces Smad signaling in melanocytes to repress PAX3, which encodes a transcription factor crucial for melanocyte differentiation. In the presence of UV radiation, a Jnk/AP-1 pathway represses TGF-beta, which together with a UV-induced p53 pathway promotes melanocyte differentiation.
Moustakas
Aristidis
A
Ludwig Institute for Cancer Research, Uppsala University, Box 595 Biomedical Center, Uppsala, Sweden. aris.moustakas@licr.uu.se
D000818:Animals; D002454:Cell Differentiation; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays
D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; C495901:TP53 protein, human; D016212:Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53