STANDARD_NAME	CHASSOT_SKIN_WOUND
SYSTEMATIC_NAME	M13038
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/CHASSOT_SKIN_WOUND
NAMESPACE	HUMAN_GENE_SYMBOL
DESCRIPTION_BRIEF	List of the transcription factors up-regulated 1 hr after wounding HDF cells (dermal fibroblasts).
DESCRIPTION_FULL	P27kip is a key inhibitory protein of the cell-cycle progression, which is rapidly downregulated in early G1 phase by a post-translational mechanism involving the proteosomal degradation. In this study, using a wounding model that induces cell-cycle entry of human dermal fibroblasts, we demonstrate that p27mRNA is downregulated when cells progress into the G1 phase, and then it returns to its basal level when cells approach the S phase. By using a quantitative polymerase chain reaction screening we identified inhibitors of differentiation (Id3), a bHLH transcriptional repressor, as a candidate mediator accounting for p27 mRNA decrease. Id3 silencing, using an small interfering RNA approach, reversed the injury mediated p27 downregulation demonstrating that Id3 is involved in the transcriptional repression of p27. Reporter gene experiments and a chromatin immunoprecipitation assay showed that Id3 likely exerts its repressive action through ELK1 inhibition. By inhibiting early p27 downregulation, Id3 depletion blocked (i) the G1-phase progression as assessed by the inhibition of pRb phosphorylation and p130 degradation and (ii) the G1/S transition as observed by the inhibition of cyclin A induction, demonstrating that p27 mRNA decrease is required for cell proliferation. Apart from its effect on the early p27 diminution, Id3 appears also involved in the control of the steady-state level of p27 at the G1/S boundary. In conclusion, this study identifies a novel mechanism of p27 regulation which besides p27 protein degradation also implicates a transcriptional mechanism mediated by Id3.
PMID	17404577
GEOID	
AUTHORS	Chassot AA,Turchi L,Virolle T,Fitsialos G,Batoz M,Deckert M,Dulic V,Meneguzzi G,Buscà R,Ponzio G
CONTRIBUTOR	Leona Saunders
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 1
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	EGR1,EGR2,EGR3,FOS,FOSB,Id3,JUN,JUNB,KLF2,NFATc2,REL
GENE_SYMBOLS	EGR1,EGR2,EGR3,FOS,FOSB,,JUN,JUNB,KLF2,,REL
FOUNDER_NAMES