KLF6 degradation after apoptotic DNA damage

Michaela S. Banck, Simon W. Beaven, Goutham Narla, Martin J. Walsh, Scott L. Friedman, Andreas S. Beutler

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Krüppel-like factor 6 (KLF6) is a cancer gene (www.sanger.ac.uk/genetics/CGP/Census/). Here, we demonstrate that KLF6 protein is rapidly degraded when apoptosis is induced via the intrinsic pathway by cisplatin, adriamycin, or UVB irradiation in multiple cell lines (HCT116, SW40, HepG2, PC3-M, Skov3, NIH-3T3, 293T, GM09706, and MEF, IMR-90). KLF6 degradation occurred in the presence or absence of p53, was associated with ubiquitination, mediated by the proteasome (half-life 16 min, unstimulated), and independent of caspases and calpain. KLF6 was unchanged by apoptosis via the extrinsic/death-receptor pathway. Deregulation of KLF6 stability may alter its tumor suppressor function and/or the response of tumors to chemotherapeutics.

Original languageEnglish (US)
Pages (from-to)6981-6986
Number of pages6
JournalFEBS Letters
Volume580
Issue number30
DOIs
StatePublished - Dec 22 2006

Keywords

  • Apoptosis
  • Cancer cells
  • Carcinogenesis
  • Chemosensitivity
  • DNA-damage
  • KLF6
  • Krüppel-like factor
  • Proteasomal degradation
  • Ubiquitin

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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