The CUL4A ubiquitin ligase is a potential therapeutic target in skin cancer and other malignancies
| Autor: | Pengbo Zhou, Jeffrey Hannah |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Skin Neoplasms
Xeroderma pigmentosum DNA Repair Carcinogenesis DNA damage DNA repair Review therapeutic targets medicine.disease_cause Proto-Oncogene Proteins p21(ras) DNA replication factor CDT1 03 medical and health sciences Drug Delivery Systems 0302 clinical medicine Neoplasms medicine Animals Humans Cell Proliferation 030304 developmental biology 0303 health sciences skin cancer biology Cell Cycle Ubiquitination Cell cycle Cullin Proteins medicine.disease 3. Good health Ubiquitin ligase DNA-Binding Proteins Oncology cullins 030220 oncology & carcinogenesis biology.protein Cancer research CUL4A cell cycle regulation |
| Zdroj: | Chinese Journal of Cancer |
| ISSN: | 1944-446X 1000-467X |
| Popis: | Cullin 4A (CUL4A) is an E3 ubiquitin ligase that directly affects DNA repair and cell cycle progression by targeting substrates including damage-specific DNA-binding protein 2 (DDB2), xeroderma pigmentosum complementation group C (XPC), chromatin licensing and DNA replication factor 1 (Cdt1), and p21. Recent work from our laboratory has shown that Cul4a-deficient mice have greatly reduced rates of ultraviolet-induced skin carcinomas. On a cellular level, Cul4a-deficient cells have great capacity for DNA repair and demonstrate a slow rate of proliferation due primarily to increased expression of DDB2 and p21, respectively. This suggests that CUL4A promotes tumorigenesis (as well as accumulation of skin damage and subsequent premature aging) by limiting DNA repair activity and expediting S phase entry. In addition, CUL4A has been found to be up-regulated via gene amplification or overexpression in breast cancers, hepatocellular carcinomas, squamous cell carcinomas, adrenocortical carcinomas, childhood medulloblastomas, and malignant pleural mesotheliomas. Because of its oncogenic activity in skin cancer and up-regulation in other malignancies, CUL4A has arisen as a potential candidate for targeted therapeutic approaches. In this review, we outline the established functions of CUL4A and discuss the E3 ligase's emergence as a potential driver of tumorigenesis. |
| Databáze: | OpenAIRE |
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