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

A. Vassilopoulos, Y. Tominaga, H. Seok Kim, T. Lahusen, B. Li, H. Yu, D. Gius, C. X. Deng*

*Corresponding author for this work

Research output: Contribution to journalArticle

10 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3023-3035
Number of pages13
JournalOncogene
Volume34
Issue number23
DOIs
StatePublished - Jun 4 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'WEE1 murine deficiency induces hyper-activation of APC/C and results in genomic instability and carcinogenesis'. Together they form a unique fingerprint.

  • Cite this