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US 12,454,559 B2Granted
Activating mitotic checkpoint control mechanisms
AssigneeThe Regents of the University of Michigan
InventorsAjit P. Joglekar, Pavithra Aravamudhan
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Abstract
Provided herein are compositions and methods for the treatment of cancer by activating the spindle assembly checkpoint (SAC) in cells. In particular, dimerized Mps1 and Spc105/KNL1 constructs are provided as tunable activators of SAC, allowing for control of chromosome segregation accuracy and prevention of aneuploidies that are common in cancer.
Claims8
A cellular or in vitro biochemical system comprising:
- (a) a polypeptide having at 95% sequence identity to a kinase domain of the wild-type Mps1 (SEQ ID NO:2) linked to a first dimerization element;
- and
- (b) a polypeptide having at 95% sequence identity to a phosphodomain of the wild-type KNL1 (SEQ ID NO:5) linked to a second dimerization element,
- wherein the kinase domain is capable of phosphorylating the phosphodomain, and
- wherein dimerization of the first dimerization element and second dimerization element facilitates phosphorylation of the KNL1 polypeptide by the Mps1 polypeptide.
2 more elements
Dependencies are inferred from the claim text.