title: The sterile alpha-motif (SAM) domain of p63 binds in vitro monoasialoganglioside (GM1) micelles.
abstract: The transcription factor p63 plays pivotal roles in epidermal barrier formation and in embryonic development. The protein structures of TAp63 and ΔNp63α isoforms include a C-terminal steril alpha-motif (SAM) involved in protein-protein 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-GM1 interaction in regulation of p63 during epidermal differentiation.
authors.affiliation: Department of Biology, University of Tor Vergata, 00133 Rome, Italy. rufini@uniroma2.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Rufini
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Lena
authors.forename: Bruno
authors.initials: B
authors.lastname: Cadot
authors.forename: Sonia
authors.initials: S
authors.lastname: Mele
authors.forename: Ivano
authors.initials: I
authors.lastname: Amelio
authors.forename: Alessandro
authors.initials: A
authors.lastname: Terrinoni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Desideri
authors.forename: Gerry
authors.initials: G
authors.lastname: Melino
authors.forename: Eleonora
authors.initials: E
authors.lastname: Candi
mesh_terms: D002236:Carbohydrate Conformation; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008823:Micelles; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary
chemical_list: C081876:CKAP4 protein, human; D008565:Membrane Proteins; D008823:Micelles; D020033:Protein Isoforms; D005677:G(M1) Ganglioside