期刊
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 81
卷 81, 期 -, 页码 561-585出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev-biochem-061611-090435
关键词
TTK; spindle checkpoint; mitosis; kinetochore; cell cycle
资金
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM083172, R01GM051312] Funding Source: NIH RePORTER
- NCI NIH HHS [CA107089] Funding Source: Medline
- NIGMS NIH HHS [R01 GM051312, GM51312, GM083172, R01 GM083172] Funding Source: Medline
MPS1 protein kinases are found widely, but not ubiquitously, in eukaryotes. This family of potentially dual-specific protein kinases is among several that regulate a number of steps of mitosis. The most widely conserved MPS1 kinase functions involve activities at the kinetochore in both the chromosome attachment and the spindle checkpoint. MPS1 kinases also function at centrosomes. Beyond mitosis, MPS1 kinases have been implicated in development, cytokinesis, and several different signaling pathways. Family members are identified by virtue of a conserved C-terminal kinase domain, though the N-terminal domain is quite divergent. The kinase domain of the human enzyme has been crystallized, revealing an unusual ATP-binding pocket. The activity, level, and subcellular localization of Mps1 family members are tightly regulated during cell-cycle progression. The mitotic functions of Mps1 kinases and their overexpression in some tumors have prompted the identification of Mps1 inhibitors and their active development as anticancer drugs.
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