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Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation

ABSTRACT: Notch signaling promotes commitment of keratinocytes to differentiation and suppresses tumorigenesis. p63, a p53 family member, has been implicated in establishment of the keratinocyte cell fate and/or maintenance of epithelial self-renewal. Here we show that p63 expression is suppressed by Notch1 activation in both mouse and human keratinocytes through a mechanism independent of cell cycle withdrawal and requiring down-modulation of selected interferon-responsive genes, including IRF7 and/or IRF3. In turn, elevated p63 expression counteracts the ability of Notch1 to restrict growth and promote differentiation. p63 functions as a selective modulator of Notch1-dependent transcription and function, with the Hes-1 gene as one of its direct negative targets. Thus, a complex cross-talk between Notch and p63 is involved in the balance between keratinocyte self-renewal and differentiation. Keywords: Notch1, p63, keratinocyte differentiation, gene expression profiling

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE5229 | GEO | 2006/07/08

SECONDARY ACCESSION(S): PRJNA96431

REPOSITORIES: GEO

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Transcription profiling of human and mouse keratinocytes infected with AD and Ad-NotchIC viruses reveals cross-regulation between Notch and p63 in keratinocyte commitment to differentiation

Project description:Notch signaling promotes commitment of keratinocytes to differentiation and suppresses tumorigenesis. p63, a p53 family member, has been implicated in establishment of the keratinocyte cell fate and/or maintenance of epithelial self-renewal. Here we show that p63 expression is suppressed by Notch1 activation in both mouse and human keratinocytes through a mechanism independent of cell cycle withdrawal and requiring down-modulation of selected interferon-responsive genes, including IRF7 and/or IRF3. In turn, elevated p63 expression counteracts the ability of Notch1 to restrict growth and promote differentiation. p63 functions as a selective modulator of Notch1-dependent transcription and function, with the Hes-1 gene as one of its direct negative targets. Thus, a complex cross-talk between Notch and p63 is involved in the balance between keratinocyte self-renewal and differentiation. Experiment Overall Design: PolyA+ mRNA (2-5 ug) from cells infected with the Ad GFP and Ad-NotchIC viruses was used as template for double stranded cDNA preparations with a T7-(dT)24 oligonucleotide primers for the first strand reaction. The resulting cDNA was used for preparation of biotin-labeled antisense cRNA and further used for hybridization to Affymetrix U74A or U95A âgene chipsâ according to the manufacturerâs recommendation.

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Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation

Project description:Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation

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Gene expression profiling of mouse prostate over-expressing the Notch1 intracellular domain.

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