Dataset Information

Greatwall kinase regulates SAC by controlling phosphorylation and activity of MPS1

ABSTRACT: The Greatwall/Mastl kinase is an essential gene, which regulates the phosphatase activity that counteracts the phosphorylation of Cdk1 substrates. Although Mastl-/- MEFs can enter mitosis, they are unable to complete mitosis due to chromosome segregation defects. Here, we show that Mastl is essential for robust spindle assembly checkpoint (SAC) maintenance. Mastl-/- MEFs display reduced phosphorylation and kinase activity of MPS1, which causes mislocalization of MPS1, Mad1, and Aurora B from the kinetochore and the inner centromere regions. This results in premature inactivation of SAC signalling and early anaphase onset without correction of chromosome-spindle attachment mistakes. Treatment of the knockout cells with protein phosphatase II inhibitor okadaic acid (OA) rescued decreased MPS1 activity, mislocalization of Aurora B, Mad1, MPS1, and premature mitotic slippage. Our data demonstrates how regulation of PP2A activity by Mastl kinase prevents premature SAC silencing as a result of controlling the phosphorylation status and activity of MPS1.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture, Fibroblast

SUBMITTER: Sheena Wee

LAB HEAD: Jayantha Gunaratne

PROVIDER: PXD004882 | Pride | 2018-10-26

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	A_120528_05_IS008_PPPep.RAW	Raw
	A_120528_06_IS008_PPPep.RAW	Raw
	A_120528_17_IS009_PPPep.RAW	Raw
	A_120528_19_IS009_PPPep.RAW	Raw
	PhosphoSTYSites.txt	Txt

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Publications

Loss of the Greatwall Kinase Weakens the Spindle Assembly Checkpoint.

Diril M Kasim MK Bisteau Xavier X Kitagawa Mayumi M Caldez Matias J MJ Wee Sheena S Gunaratne Jayantha J Lee Sang Hyun SH Kaldis Philipp P

PLoS genetics 20160915 9

The Greatwall kinase/Mastl is an essential gene that indirectly inhibits the phosphatase activity toward mitotic Cdk1 substrates. Here we show that although Mastl knockout (MastlNULL) MEFs enter mitosis, they progress through mitosis without completing cytokinesis despite the presence of misaligned chromosomes, which causes chromosome segregation defects. Furthermore, we uncover the requirement of Mastl for robust spindle assembly checkpoint (SAC) maintenance since the duration of mitotic arrest ...[more]

PMID: 27631493

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