p51/p63 Controls subunit alpha3 of the major epidermis integrin anchoring the stem cells to the niche.
p51/p63, a member of the tumor suppressor p53 gene family, is crucial for skin development. We describe here identification of ITGA3 encoding integrin alpha(3) as a target of its trans-activating function, proposing that p51/p63 allows epidermal stem cells to express laminin receptor alpha(3)beta(1) for anchorage to the basement membrane. When activated by genotoxic stress or overexpressed ectopically in non-adherent cells, p51/p63 transduced a phenotype to attach to extracellular matrices, which was accompanied by expression of ITGA3. Motifs matching the p53-binding consensus sequence were located in a scattered form in intron 1 of human ITGA3, and served as p51/p63-responsive elements in reporter assays. In addition to the trans-activating ability of the TA isoform, we detected a positive effect of the DeltaN isoform on ITGA3. The high level alpha(3) production in human keratinocyte stem cells diminished upon elimination of p51/p63 by small interfering RNA or by Ca(2+)-induced differentiation. Furthermore, a chromatin immunoprecipitation experiment indicated a physical interaction of p51/p63 with intron 1 of ITGA3. This study provides a molecular basis for the standing hypothesis that p51/p63 is essential for epidermal-mesenchymal interactions.
Kurata
Shun-Ichi
S
Department of Biochemical Genetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510 Japan.
Okuyama
Takeshi
T
Osada
Motonobu
M
Watanabe
Tatsuya
T
Tomimori
Yoshiya
Y
Sato
Shingo
S
Iwai
Aki
A
Tsuji
Tsutomu
T
Ikawa
Yoji
Y
Katoh
Iyoko
I
D004268:DNA-Binding Proteins; D004817:Epidermis / Q000196:embryology / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D006801:Humans; D039422:Integrin alpha3 / Q000235:genetics / Q000378:metabolism*; D007438:Introns; D008648:Mesoderm / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D011233:Precipitin Tests; D017422:Sequence Analysis, DNA; D013234:Stem Cells / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D039422:Integrin alpha3; D010750:Phosphoproteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins