Lena Anna Maria, Duca Sara, Novelli Flavia, Melino Sonia, Annicchiarico-Petruzzelli Margherita, Melino Gerry, Candi Eleonora
Department of Experimental Medicine and Surgery, University of "Tor Vergata", Rome, Italy.
Department of Chemistry, University of "Tor Vergata", Rome, Italy.
Biochem Biophys Res Commun. 2015 Nov 13;467(2):434-40. doi: 10.1016/j.bbrc.2015.09.111. Epub 2015 Sep 25.
p63, a member of the p53 family, is a crucial transcription factor for epithelial development and skin homeostasis. Heterozygous mutations in TP63 gene have been associated with human ectodermal dysplasia disorders. Most of these TP63 mutations are missense mutations causing amino acidic substitutions at p63 DNA binding or SAM domains that reduce or abolish the transcriptional activity of mutants p63. A significant number of mutants, however, resides in part of the p63 protein that apparently do not affect DNA binding and/or transcriptional activity, such as the N-terminal domain. Here, we characterize five p63 mutations at the 5' end of TP63 gene aiming to understand the pathogenesis of the diseases and to uncover the role of ΔNp63α N-terminus residues in determining its transactivation potential.
p63是p53家族的一员，是上皮发育和皮肤稳态的关键转录因子。TP63基因的杂合突变与人类外胚层发育异常疾病有关。这些TP63突变大多是错义突变，导致p63 DNA结合或SAM结构域的氨基酸替换，从而降低或消除突变型p63的转录活性。然而，相当数量的突变体存在于p63蛋白的部分区域，这些区域显然不影响DNA结合和/或转录活性，如N端结构域。在这里，我们对TP63基因5'端的五个p63突变进行了表征，旨在了解疾病的发病机制，并揭示ΔNp63α N端残基在决定其反式激活潜能中的作用。
