Making sense of Cbp/p300 loss of function mutations in skin tumorigenesis
| Autor: | Stefano Alemà, Sergio Anastasi, Oreste Segatto |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Skin Neoplasms Carcinogenesis DNA repair Transgene Biology medicine.disease_cause Pathology and Forensic Medicine Mice 03 medical and health sciences 0302 clinical medicine Loss of Function Mutation medicine Animals Humans p300-CBP Transcription Factors HRAS Loss function Histone Acetyltransferases DNA synthesis Phenotype United Kingdom 030104 developmental biology 030220 oncology & carcinogenesis Mutation Carcinoma Squamous Cell Cancer research |
| Zdroj: | The Journal of Pathology. 250:3-6 |
| ISSN: | 1096-9896 0022-3417 |
| DOI: | 10.1002/path.5336 |
| Popis: | CBP and p300 are highly homologous lysine acetyltransferases involved in cell cycle regulation, DNA synthesis and DNA repair. Loss of function mutations of CBP and p300 are found in about one-third of cutaneous squamous cell carcinoma (cSCC) and often co-occur, yet their role in cSCC pathogenesis is unclear. Writing in The Journal of Pathology, Ichise and colleagues modeled combined heterozygous loss of Cbp/p300 in mouse keratinocytes expressing a transgenic HrasS35 allele that allows selective coupling of Hras to the Erk pathway. Epidermal thickening caused by expression of HrasS35 was exacerbated by reduced dosage of Cbp/p300 and eventually resulted in development of skin papillomas. This phenotype was associated with reduced expression of Mig6, an Egfr feedback inhibitor, and attendant enhancement of Egfr signaling to the Ras-Erk pathway. This model provides a mechanistic framework for understanding how Cbp/p300 loss of function mutations impact on skin tumorigenesis and suggests potential therapeutic options in CBP/p300 mutated human cSCC. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
| Databáze: | OpenAIRE |
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