Kinase Signaling in the Spindle Checkpoint

Abstract

The spindle checkpoint is a cell cycle surveillance system that ensures the fidelity of chromosome segregation. In mitosis, it elicits the "wait anaphase" signal to inhibit the anaphase-promoting complex or cyclosome until all chromosomes achieve bipolar microtubule attachment and align at the metaphase plate. Because a single kinetochore unattached to microtubules activates the checkpoint, the wait anaphase signal is thought to be generated by this kinetochore and is then amplified and distributed throughout the cell to inhibit the anaphase-promoting complex/cyclosome. Several spindle checkpoint kinases participate in the generation and amplification of this signal. Recent studies have begun to reveal the activation mechanisms of these checkpoint kinases. Increasing evidence also indicates that the checkpoint kinases not only help to generate the wait anaphase signal but also actively correct kinetochore-microtubule attachment defects.

Protein Phosphatase 1 Regulates Exit from the Spindle Checkpoint in Budding Yeast

“…One possibility is that Ipl1/Aurora is required for all spindle checkpoint responses in budding yeast, but its role in the response to attachment defects has not been detected because it is necessary to use conditional mutants that retain residual function [22]. An alternative, and not mutually exclusive possibility, is that Glc7 overexpression reverses the phosphorylation of kinases in addition to Ipl1/Aurora, consistent with the requirement for multiple kinases in spindle checkpoint activation [5]. …”

“…The target of the checkpoint is the Cdc20 protein that initiates the anaphase promoting complex (APC)-dependent degradation of the anaphase inhibitor Pds1/securin [4]. Although the molecular details of spindle checkpoint activation are still being elucidated, phosphorylation by at least four kinases is a crucial requirement [5]. However, less is known about the mechanisms that silence the checkpoint once kinetochores biorient.…”

The Composition, Functions, and Regulation of the Budding Yeast Kinetochore

“…A key feature of the checkpoint is regulation by phosphorylation (Kang and Yu 2009). Mps1 phosphorylation of Spc105 is essential for the checkpoint (London et al 2012;Shepperd et al 2012;Yamagishi et al 2012).…”

Arabidopsis Cell Division Cycle 20.1 Is Required for Normal Meiotic Spindle Assembly and Chromosome Segregation

“…Correction of mistakes in kinetochore attachment to the spindle releases CDC20, which then activates APC/C for the removal of cohesin, thus promoting entry into anaphase (Salah and Nasmyth, 2000;Singh et al, 2014). In mitosis, the SAC proteins, including the protein kinase Aurora B, are recruited to unattached kinetochores to delay chromosome segregation until all chromosomes are correctly attached to the bipolar spindle (Kang and Yu, 2009;Zich and Hardwick, 2010). In animal cell lines and yeast, the centromeric localization of Aurora B depends on phosphorylation of Thr-3 on histone H3 (H3T3ph), which is mediated by Haspin (Dai et al, 2005;Kelly et al, 2010;Wang et al, 2010;F.…”