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WEE1 murine deficiency induces hyper-activation of APC/C and results in genomic instability and carcinogenesis

Title
WEE1 murine deficiency induces hyper-activation of APC/C and results in genomic instability and carcinogenesis
Authors
Vassilopoulos, A.Tominaga, Y.Kim, H-SeokLahusen, T.Li, B.Yu, H.Gius, D.Deng, C-X
Ewha Authors
김현석
SCOPUS Author ID
김현석scopus
Issue Date
2015
Journal Title
ONCOGENE
ISSN
0950-9232JCR Link1476-5594JCR Link
Citation
vol. 34, no. 23, pp. 3023 - 3035
Publisher
NATURE PUBLISHING GROUP
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
The tyrosine kinase WEE1 controls the timing of entry into mitosis in eukaryotes and its genetic deletion leads to pre-implantation lethality in mice. Here, we show that besides the premature mitotic entry phenotype, Wee1 mutant murine cells fail to complete mitosis properly and exhibit several additional defects that contribute to the deregulation of mitosis, allowing mutant cells to progress through mitosis at the expense of genomic integrity. WEE1 interacts with the anaphase promoting complex, functioning as a negative regulator, and the deletion of Wee1 results in hyper-activation of this complex. Mammary specific knockout mice overcome the DNA damage response pathway triggered by the mis-coordination of the cell cycle in mammary epithelial cells and heterozygote mice spontaneously develop mammary tumors. Thus, WEE1 functions as a haploinsufficient tumor suppressor that coordinates distinct cell division events to allow correct segregation of genetic information into daughter cells and maintain genome integrity.
DOI
10.1038/onc.2014.239
Appears in Collections:
일반대학원 > 바이오융합과학과 > Journal papers
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