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.

中文翻译：

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在皮肤肿瘤发生过程中了解Cbp / p300功能缺失的突变。

CBP和p300是高度同源的赖氨酸乙酰基转移酶，参与细胞周期调节，DNA合成和DNA修复。在大约三分之一的皮肤鳞状细胞癌（cSCC）中发现了CBP和p300的功能突变，这些突变通常同时发生，但尚不清楚它们在cSCC发病机理中的作用。Ichise及其同事在《病理学杂志》（The Journal of Pathology）中发表文章，对表达转基因HrasS35等位基因的小鼠角质形成细胞中Cbp / p300的杂合性杂合损失进行了建模，该基因允许Hras与Erk途径选择性偶联。减少Cbp / p300的剂量会加剧由HrasS35表达引起的表皮增厚，并最终导致皮肤乳头状瘤的发展。该表型与Eigfr反馈抑制剂Mig6的表达降低以及伴随的Egfr信号向Ras-Erk途径的增强有关。该模型为理解Cbp / p300功能缺失突变对皮肤肿瘤发生的影响提供了机制框架，并提出了在CBP / p300突变的人cSCC中的潜在治疗选择。©2019英国和爱尔兰病理学会。由John Wiley＆Sons，Ltd.出版