Conforti, F, Yang, AL, Piro, MC, Mellone, M, Terrinoni, A, Candi, E, Tucci, P, Thomas, GJ, Knight, RA, Melino, G and Sayan, BS 
ORCID: https://orcid.org/0000-0003-2305-1970
2012,
'PIR2/Rnf144B regulates epithelial homeostasis by mediating degradation of p21 WAF1 and p63'
, Oncogene, 32
.
Abstract
ΔNp63 is a transcription factor that is critical for the development of stratified epithelia and is overexpressed or amplified in >80% of squamous cell carcinomas (SCCs). We identified the RING finger E3 ubiquitin ligase PIR2/Rnf144b as a direct transcriptional target of ΔNp63α and showed that its expression parallels that of ΔNp63α in keratinocytes, SCC cell lines and SCCs. We used primary keratinocytes as a model system to investigate the function of PIR2/Rnf144b in stratified epithelia. Depletion of PIR2/Rnf144b severely impaired keratinocyte proliferation and differentiation, associated with accumulation of p21WAF1/CIP1; a known target of PIR2/Rnf144b. More importantly, we found that PIR2/Rnf144b binds and mediates proteasomal degradation of ΔNp63α, generating a hitherto unknown auto-regulatory feedback loop. These findings substantiate PIR2/Rnf144b as a potentially critical component of epithelial homeostasis, acting downstream of ΔNp63α to regulate cellular levels of p21WAF1/CIP1 and ΔNp63α.
| Item Type: | Article |
|---|---|
| Schools: | Schools > School of Environment and Life Sciences |
| Journal or Publication Title: | Oncogene |
| Publisher: | Springer Nature |
| ISSN: | 0950-9232 |
| Depositing User: | BS Sayan |
| Date Deposited: | 08 Feb 2023 13:47 |
| Last Modified: | 08 Feb 2023 13:47 |
| URI: | https://usir.salford.ac.uk/id/eprint/66331 |
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