p63 is upstream of IKK alpha in epidermal development.
The epidermis, the outer layer of the skin composed of keratinocytes, develops following the action of the transcription factor p63. The mouse Trp63 gene contains two promoters, driving the production of distinct proteins, one with an N-terminal trans-activation domain (TAp63) and one without (DeltaNp63), although their relative contribution to epidermal development is not clearly established. To identify the relative role of p63 isoforms in relation to IKKalpha, also known to be essential for epithelial development, we performed both molecular and in vivo analyses using genetic complementation in mice. We found that the action of TAp63 is mediated at the molecular level by direct and indirect transactivation of IKKalpha and Ets-1, respectively. We also found that DeltaNp63 upregulates IKKalpha indirectly, through GATA-3. Our data are consistent with a role for p63 directly upstream of IKKalpha in epithelial development.
Candi
Eleonora
E
Biochemistry Laboratory, IDI-IRCCS, University of Rome Tor Vergata, 00133 Rome, Italy. candi@uniroma2.it
Terrinoni
Alessandro
A
Rufini
Alessandro
A
Chikh
Anissa
A
Lena
Anna Maria
AM
Suzuki
Yasuhiro
Y
Sayan
Berna S
BS
Knight
Richard A
RA
Melino
Gerry
G
D000818:Animals; D045744:Cell Line, Tumor; D004817:Epidermis / Q000378:metabolism / Q000502:physiology*; D050990:GATA3 Transcription Factor / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation
D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D010750:Phosphoproteins; D020033:Protein Isoforms; D050784:Proto-Oncogene Protein c-ets-1; D015534:Trans-Activators; C486419:Trp63 protein, mouse; C496559:CHUK protein, human; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase