Transcriptional repression of WEE1 by Kruppel-like factor 2 is involved in DNA damage-induced apoptosis

Fang Wang, Yu Zhu, Yan Huang, Sarah McAvoy, William B. Johnson, Tak Hong Cheung, Tony Kwok Hung Chung, Keith Wing Kit Lo, So Fan Yim, May M Y Yu, Hextan Y S Ngan, Yick Fu Wong, David I Smith

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Human Kruppel-like factor 2 (KLF2) is a Cys2/His2 zinc-finger-containing transcriptional factor, which is involved in multiple cellular pathways. Utilizing gene expression profiling to identify aberrantly expressed genes in ovarian cancer, we found that KLF2 was significantly and specifically downregulated in ovarian tumors. After reintroducing KLF2 into ovarian cancer cell lines, we observed decreased cell growth and increased sensitivity to DNA damage-induced apoptosis. Analysis of genes that could be potential targets of KLF2 revealed that KLF2 negatively regulated WEE1 expression. WEE1 encodes a tyrosine kinase that regulates the G2/M cell cycle transition. Expression of KLF2 markedly repressed the transcription of WEE1 by directly binding to an SP1/CPBP motif located between -252bp and the start codon of the WEE1 promoter. Both activation and zinc-finger domains of KLF2 were required for this suppression of Wee1 expression. In addition, we demonstrated that Wee1 expression prevents cancer cells from undergoing apoptosis in response to DNA damage; however, this resistance was abolished by coexpression of KLF2, which inhibits WEE1 transcription. Thus, the level of WEE1 is regulated by KLF2 and enhanced KLF2 expression sensitizes cells to DNA damage-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)3875-3885
Number of pages11
JournalOncogene
Volume24
Issue number24
DOIs
StatePublished - Jun 2 2005

Fingerprint

Kruppel-Like Transcription Factors
DNA Damage
Apoptosis
Zinc Fingers
Ovarian Neoplasms
Initiator Codon
Gene Expression Profiling
Protein-Tyrosine Kinases
Genes
Neoplasms
Cell Cycle
Down-Regulation

Keywords

  • KLF2
  • Transcriptional regulation
  • WEE1

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Transcriptional repression of WEE1 by Kruppel-like factor 2 is involved in DNA damage-induced apoptosis. / Wang, Fang; Zhu, Yu; Huang, Yan; McAvoy, Sarah; Johnson, William B.; Cheung, Tak Hong; Chung, Tony Kwok Hung; Lo, Keith Wing Kit; Yim, So Fan; Yu, May M Y; Ngan, Hextan Y S; Wong, Yick Fu; Smith, David I.

In: Oncogene, Vol. 24, No. 24, 02.06.2005, p. 3875-3885.

Research output: Contribution to journalArticle

Wang, F, Zhu, Y, Huang, Y, McAvoy, S, Johnson, WB, Cheung, TH, Chung, TKH, Lo, KWK, Yim, SF, Yu, MMY, Ngan, HYS, Wong, YF & Smith, DI 2005, 'Transcriptional repression of WEE1 by Kruppel-like factor 2 is involved in DNA damage-induced apoptosis', Oncogene, vol. 24, no. 24, pp. 3875-3885. https://doi.org/10.1038/sj.onc.1208546
Wang, Fang ; Zhu, Yu ; Huang, Yan ; McAvoy, Sarah ; Johnson, William B. ; Cheung, Tak Hong ; Chung, Tony Kwok Hung ; Lo, Keith Wing Kit ; Yim, So Fan ; Yu, May M Y ; Ngan, Hextan Y S ; Wong, Yick Fu ; Smith, David I. / Transcriptional repression of WEE1 by Kruppel-like factor 2 is involved in DNA damage-induced apoptosis. In: Oncogene. 2005 ; Vol. 24, No. 24. pp. 3875-3885.
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