TY  - JOUR
AU  - Rathi, Siddhi
AU  - Polat, Irem
AU  - Pereira, Gislene
TI  - The budding yeast GSK-3 homologue Mck1 is an essential component of the spindle position checkpoint.
JO  - Open biology
VL  - 12
IS  - 11
SN  - 2046-2441
CY  - London
PB  - Royal Society Publishing
M1  - DKFZ-2022-02641
SP  - 220203
PY  - 2022
N1  - DKFZ-ZMBH Alliance / #LA:A180#
AB  - The spindle position checkpoint (SPOC) is a mitotic surveillance mechanism in Saccharomyces cerevisiae that prevents cells from completing mitosis in response to spindle misalignment, thereby contributing to genomic integrity. The kinase Kin4, one of the most downstream SPOC components, is essential to stop the mitotic exit network (MEN), a signalling pathway that promotes the exit from mitosis and cell division. Previous work, however, suggested that a Kin4-independent pathway contributes to SPOC, yet the underlying mechanisms remain elusive. Here, we established the glycogen-synthase-kinase-3 (GSK-3) homologue Mck1, as a novel component that works independently of Kin4 to engage SPOC. Our data indicate that both Kin4 and Mck1 work in parallel to counteract MEN activation by the Cdc14 early anaphase release (FEAR) network. We show that Mck1's function in SPOC is mediated by the pre-replication complex protein and mitotic cyclin-dependent kinase (M-Cdk) inhibitor, Cdc6, which is degraded in a Mck1-dependent manner prior to mitosis. Moderate overproduction of Cdc6 phenocopies MCK1 deletion and causes SPOC deficiency via its N-terminal, M-Cdk inhibitory domain. Our data uncover an unprecedented role of GSK-3 kinases in coordinating spindle orientation with cell cycle progression.
KW  - Humans
KW  - Saccharomyces cerevisiae Proteins: genetics
KW  - Glycogen Synthase Kinase 3: genetics
KW  - Glycogen Synthase Kinase 3: metabolism
KW  - Spindle Apparatus: metabolism
KW  - Saccharomycetales: metabolism
KW  - Protein Serine-Threonine Kinases
KW  - Phosphorylation
KW  - Saccharomyces cerevisiae: genetics
KW  - Mitosis
KW  - Cell Cycle Proteins: metabolism
KW  - Protein Tyrosine Phosphatases: genetics
KW  - Protein Tyrosine Phosphatases: metabolism
KW  - Cdc6 (Other)
KW  - MCK1 (Other)
KW  - budding yeast (Other)
KW  - cell division (Other)
KW  - checkpoint control (Other)
KW  - mitotic exit (Other)
KW  - Saccharomyces cerevisiae Proteins (NLM Chemicals)
KW  - Glycogen Synthase Kinase 3 (NLM Chemicals)
KW  - Protein Serine-Threonine Kinases (NLM Chemicals)
KW  - Cell Cycle Proteins (NLM Chemicals)
KW  - CDC14 protein, S cerevisiae (NLM Chemicals)
KW  - Protein Tyrosine Phosphatases (NLM Chemicals)
KW  - MCK1 protein, S cerevisiae (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:36321416
DO  - DOI:10.1098/rsob.220203
UR  - https://inrepo02.dkfz.de/record/182432
ER  -