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Publication : p51/p63 Controls subunit alpha3 of the major epidermis integrin anchoring the stem cells to the niche.

First Author  Kurata S Year  2004
Journal  J Biol Chem Volume  279
Issue  48 Pages  50069-77
PubMed ID  15361520 Mgi Jnum  J:94980
Mgi Id  MGI:3522396 Doi  10.1074/jbc.M406322200
Citation  Kurata S, et al. (2004) p51/p63 Controls subunit alpha3 of the major epidermis integrin anchoring the stem cells to the niche. J Biol Chem 279(48):50069-77
abstractText  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.
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