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Human CDK12 and CDK13, multi-tasking CTD kinases for the new millennium

机译：人类CDK12和CDK13，用于新千年的多任务CTD激酶

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摘要

As the new millennium began, CDK12 and CDK13 were discovered as nucleotide sequences that encode protein kinases related to cell cycle CDKs. By the end of the first decade both proteins had been qualified as CTD kinases, and it was emerging that bothare heterodimers containing a Cyclin K subunit. Since then, many studies on CDK12 have shown that, through phosphorylating the CTD of transcribing RNAPII, it plays critical roles in several stages of gene expression, notably RNA processing; it is also crucial for maintaining genome stability. Fewer studies on CKD13 have clearly shown that it is functionally distinct from CDK12. CDK13 is important for proper expression of a number of genes, but it also probably plays yet-to-be-discovered roles in other processes. This review summarizes much of the work on CDK12 and CDK13 and attempts to evaluate the results and place them in context. Our understanding of these two enzymes has begun to mature, but we still have much to learn about both. An indicator of one major area of medically-relevant future research comes from the discovery that CDK12 is a tumor suppressor, notably for certain ovarian and prostate cancers. A challenge for the future is to understand CDK12 and CDK13 well enough to explain how theirloss promotes cancer development and how we can intercede to prevent or treat those cancers.
机译：由于新千年开始，CDK12和CDK13被发现为编码与细胞周期CDK相关的蛋白激酶的核苷酸序列。到第一个十年结束时，两种蛋白质都被称为CTD激酶，并促使含有细胞周期蛋白K亚基的异二聚体。从那时起，许多关于CDK12的研究表明，通过磷酸化转录RNAPII的CTD，它在基因表达的几个阶段中起重要作用，特别是RNA加工;它对于维持基因组稳定性也至关重要。对CKD13的研究较少明确表明它与CDK12有着功能性不同。 CDK13对于适当表达许多基因的表达很重要，但它也可能在其他过程中发挥令人遗憾的作用。此审查总结了CDK12和CDK13上的大部分工作，并尝试评估结果并将其放在上下文中。我们对这两种酶的理解已经开始成熟，但我们仍然有很多东西要了解两者。一个主要的医学未来研究领域的指标来自发现CDK12是肿瘤抑制剂，特别是对于某些卵巢和前列腺癌。对未来的挑战是了解CDK12和CDK13，足以解释他们的血统如何促进癌症发展以及我们如何倾向于预防或治疗这些癌症。

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