Roles for MDC1 in cancer development and treatment.
Roles for MDC1 in cancer development and treatment.
复制标题
DOI：
10.1016/j.dnarep.2020.102948
复制
发表时间：
2020-11
期刊：
影响因子：
3.8
通讯作者：
Huang TT
中科院分区：
文献类型：
--
作者：
Ruff SE;Logan SK;Garabedian MJ;Huang TT
DNA损伤反应（DDR）是维持基因组完整性和防止致癌突变积累所必需的。因此，参与DDR的蛋白质通常充当肿瘤抑制剂，执行保持DNA保真度完整的关键任务。DNA损伤检查点介导因子1（Mediator of DNA damage checkpoint 1，MDC 1）是一种参与DDR早期步骤的支架蛋白。MDC 1直接与γ-H2 AX相互作用，γ-H2 AX是H2 AX的磷酸化形式，是DNA损伤的常用标记。然后，它通过募集ATM激酶来传播H2 AX的磷酸化。虽然以前已经审查了MDC 1在DDR中的功能，但尚未审查其在癌症中的作用，并且许多研究最近已经确定了MDC 1与致癌作用之间的联系。这包括MDC 1作为肿瘤抑制因子发挥作用，其损失作为癌症的生物标志物并促进药物敏感性。研究还表明，MDC 1在DDR中的作用超出了其传统作用，并作为核受体转录活性的共调节因子发挥作用，并且MDC 1中的突变存在于肿瘤中，也可能导致生殖系癌症易感性。本综述将讨论MDC 1与癌症的联系，并确定MDC 1在肿瘤形成，进展和治疗中的重要作用。我们还讨论了MDC 1水平调节的机制以及这如何有助于肿瘤形成。
The DNA damage response (DDR) is necessary to maintain genome integrity and prevent the accumulation of oncogenic mutations. Consequently, proteins involved in the DDR often serve as tumor suppressors, carrying out the crucial task of keeping DNA fidelity intact. Mediator of DNA damage checkpoint 1 (MDC1) is a scaffold protein involved in the early steps of the DDR. MDC1 interacts directly with γ-H2AX, the phosphorylated form of H2AX, a commonly used marker for DNA damage. It then propagates the phosphorylation of H2AX by recruiting ATM kinase. While the function of MDC1 in the DDR has been reviewed previously, its role in cancer has not been reviewed, and numerous studies have recently identified a link between MDC1 and carcinogenesis. This includes MDC1 functioning as a tumor suppressor, with its loss serving as a biomarker for cancer and contributor to drug sensitivity. Studies also indicate that MDC1 operates outside of its traditional role in DDR, and functions as a co-regulator of nuclear receptor transcriptional activity, and that mutations in MDC1 are present in tumors and can also cause germline predisposition to cancer. This review will discuss reports that link MDC1 to cancer and identify MDC1 as an important player in tumor formation, progression, and treatment. We also discuss mechanisms by which MDC1 levels are regulated and how this contributes to tumor formation.
登录
查看更多内容
影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
56.9
作者：
Celeste, A;Petersen, S;Nussenzweig, A
通讯作者：
Nussenzweig, A
影响因子：
82.9
作者：
Beltran H;Prandi D;Mosquera JM;Benelli M;Puca L;Cyrta J;Marotz C;Giannopoulou E;Chakravarthi BV;Varambally S;Tomlins SA;Nanus DM;Tagawa ST;Van Allen EM;Elemento O;Sboner A;Garraway LA;Rubin MA;Demichelis F
通讯作者：
Demichelis F
影响因子：
5.2
作者：
Chen Y;Williams V;Filippova M;Filippov V;Duerksen-Hughes P
通讯作者：
Duerksen-Hughes P
影响因子：
64.5
作者：
Celeste, A;Difilippantonio, S;Nussenzweig, A
通讯作者：
Nussenzweig, A