The sterile alpha-motif (SAM) domain of p63 binds in vitro monoasialoganglioside (GM1) micelles

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• 作者：Stefano Rufini^a ;   ; ^{rufini@uniroma2.it} ; Anna Maria Lena^b ; Bruno Cadot^b ; Sonia Mele^a ; Ivano Amelio^b ; Alessandro Terrinoni^c ; Alessandro Desideri^a ; Gerry Melino^b ;   ; ^c ; Eleonora Candi^b ;   ; ^{candi@uniroma2.it}
• 关键词：p63 ; Ganglioside ; Keratinocytes ; Skin ; SAM domain
• 刊名：Biochemical Pharmacology
• 出版年：2011
• 出版时间：15 November 2011
• 年：2011
• 卷：82
• 期：10
• 页码：1262-1268
• 全文大小：842 K

文摘

The transcription factor p63 plays pivotal roles in epidermal barrier formation and in embryonic development. The protein structures of TAp63 and ¦¤Np63¦Á isoforms include a C-terminal steril alpha-motif (SAM) involved in protein¨Cprotein interaction. Identification of p63 SAM domain interactors could lead to the explanation of novel mechanisms of regulation of p63 activity, possibly relevant in the physiological role of p63 and in genetic disorders associated with mutations of the p63 gene. In this work, we have performed a biochemical analysis of p63 SAM domain preferences in lipid binding. We have identified the ganglioside GM1 as a high affinity interactor, capable of modulating p63 transcriptional ability exclusively on epidermal target genes. In agreement with these data we report a consistent expression profile and localization analysis of p63 and GM1 in primary keratinocytes and in human epidermal biopsies. Therefore, we propose a potential biological role of p63¨CGM1 interaction in regulation of p63 during epidermal differentiation.