Dataset Information

The Greatwall kinase safeguards the genome integrity by balancing the kinome activity in mitosis.

ABSTRACT: Mastl is commonly overexpressed in cancer, appearing as an alternative therapeutic anticancer target. Loss of Mastl induces multiple chromosomal mitotic errors that lead to the accumulation of micronuclei and multilobulated cells with polyploidy. Our detailed analyses display that loss of Mastl quickly lead to chromosomes breakage and abnormalities impairing correct segregation. Phosphoproteomic data of mouse embryonic fibroblasts revealed defects in kinetochores, perichromosomes, and centrosomes but also on RNA binding proteins and double strand DNA damage repair.In our study, Rad51ap1, a well-known homologous recombination regulator, appeared to be effectively phosphorylated by Nek2 and CDK1, but also efficiently depshosphorylated by PP2A/B55. Taken together, these results suggest that Mastl loss induces a multitude of alteration even in noncancerous cells that lead to the disruption of DNA damage repair triggering chromosomes breakage and in consequence, creates an accumulative disequilibrium in the phosphoproteome.

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Xavier Bisteau

PROVIDER: PXD019297 | JPOST Repository | Thu Oct 15 00:00:00 BST 2020

REPOSITORIES: jPOST

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Dataset's files

Source:

			Action	DRS
	20160802_RS_XB_1_phos_mini.raw	Raw
	20160804_RS_XB_phospho_1_1.raw	Raw
	20160804_RS_XB_phospho_1_2.raw	Raw
	20160804_RS_XB_phospho_1_3.raw	Raw
	20160804_RS_XB_phospho_1_4.raw	Raw

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Publications

The Greatwall kinase safeguards the genome integrity by affecting the kinome activity in mitosis.

Bisteau Xavier X Lee Joann J Srinivas Vinayaka V Lee Joanna H S JHS Niska-Blakie Joanna J Tan Gifford G Yap Shannon Y X SYX Hom Kevin W KW Wong Cheng Kit CK Chae Jeongjun J Wang Loo Chien LC Kim Jinho J Rancati Giulia G Sobota Radoslaw M RM Tan Chris S H CSH Kaldis Philipp P

Oncogene 20200925 44

Progression through mitosis is balanced by the timely regulation of phosphorylation and dephosphorylation events ensuring the correct segregation of chromosomes before cytokinesis. This balance is regulated by the opposing actions of CDK1 and PP2A, as well as the Greatwall kinase/MASTL. MASTL is commonly overexpressed in cancer, which makes it a potential therapeutic anticancer target. Loss of Mastl induces multiple chromosomal errors that lead to the accumulation of micronuclei and multilobulat ...[more]

PMID: 32978522

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