p53 homologue, p51/p63, maintains the immaturity of keratinocyte stem cells by inhibiting Notch1 activity
| Autor: | Shuntaro Ikawa, Eisaku Ogawa, Setsuya Aiba, Hachiro Tagami, Hirokazu Nagoshi, Tadashi Terui, Ryuhei Okuyama, Akira Kurihara, Masuo Obinata, M Yabuki |
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| Rok vydání: | 2007 |
| Předmět: |
Keratinocytes
Cancer Research Cell signaling Tumor suppressor gene Biology Transfection medicine.disease_cause Mice Genetics medicine Animals Protein Isoforms Receptor Notch1 Molecular Biology Cells Cultured Cell Proliferation Stem Cells Cell Differentiation Genes p53 Phosphoproteins stomatognathic diseases medicine.anatomical_structure embryonic structures Trans-Activators cardiovascular system Cancer research sense organs biological phenomena cell phenomena and immunity Stem cell Carcinogenesis Keratinocyte |
| Zdroj: | Oncogene. 26:4478-4488 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1210235 |
| Popis: | p53 homologue, p51/p63, predominantly expressed in keratinocyte stem cells, is indispensable for the formation of epidermis. Notch1, another such gene indispensable for the process, induces growth arrest and differentiation in keratinocytes. We found that exogenous expression of DeltaNp51B (DeltaNp63alpha), one of the isoforms of p51 specifically expressed in basal keratinocytes, blocked Notch 1-dependent growth arrest and differentiation in mouse keratinocytes by inhibiting p21 expression and maintaining integrins expression. Furthermore, DeltaNp51B by itself was found to have ability to induce expression of integrin alpha6beta4, which promotes attachment of basal cells to basal membrane thereby keeping the cells in immature state. Therefore, we conclude that DeltaNp51B expression warrants integrin expression even under the influence of Notch1 and that DeltaNp51B is a long-sought factor required to maintain basal cell keratinocytes immaturity by inhibiting Notch1 activity. We will postulate a plausible model explaining the maintenance of the squamous epithelium architectures as well as offering mechanistic explanations for pathological features of skin diseases, including cancers, psoriasis along with physiological wound healings. |
| Databáze: | OpenAIRE |
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