p63 regulates proliferation and differentiation of developmentally mature keratinocytes

p63 is a multi-isoform p53 family member required for epidermal development. Contrasting roles for p63 in either the initial commitment to the stratified epithelial cell fate or in stem cell-based self-renewal have been proposed. To investigate p63 function in a post-developmental context, we used s...

Full description

Saved in:
Bibliographic Details
Published in:Genes & development 2006-11, Vol.20 (22), p.3185-3197
Main Authors: Truong, Amy B, Kretz, Markus, Ridky, Todd W, Kimmel, Robin, Khavari, Paul A
Format: Article
Language:English
Subjects:
Cell Cycle
Cell Differentiation
Cell Proliferation
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Down-Regulation
Epidermis - cytology
Humans
Keratinocytes - cytology
Keratinocytes - physiology
Protein Isoforms - metabolism
Research Paper
RNA, Messenger - genetics
RNA, Messenger - metabolism
Trans-Activators - genetics
Trans-Activators - metabolism
Transcription Factors
Tumor Suppressor Protein p53 - deficiency
Tumor Suppressor Protein p53 - metabolism
Tumor Suppressor Proteins - genetics
Tumor Suppressor Proteins - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:p63 is a multi-isoform p53 family member required for epidermal development. Contrasting roles for p63 in either the initial commitment to the stratified epithelial cell fate or in stem cell-based self-renewal have been proposed. To investigate p63 function in a post-developmental context, we used siRNAs directed against p63 to down-regulate p63 expression in regenerating human epidermis. Loss of p63 resulted in severe tissue hypoplasia and inhibited both stratification and differentiation in a cell-autonomous manner. Although p63-deficient cells exhibited hypoproliferation, differentiation defects were not due to tissue hypoplasia. Simultaneous p63 and p53 knockdown rescued the cell proliferation defect of p63 knockdown alone but failed to restore differentiation, suggesting that defects in epidermal proliferation and differentiation are mediated via p53-dependent and -independent mechanisms, respectively. Furthermore, DeltaNp63 isoforms are the main mediators of p63 effects, although TAp63 isoforms may contribute to late differentiation. These data indicate that p63 is required for both the proliferative and differentiation potential of developmentally mature keratinocytes.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.1463206