Fanconi anemia D2 protein is an apoptotic target mediated by caspases

Su Jung Park, Brian D. Beck, M. Reza Saadatzadeh, Laura Haneline, D. Clapp, Suk-Hee Lee

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

FANCD2, a key factor in the FANC-BRCA1 pathway is monoubiquitinated and targeted to discrete nuclear foci following DNA damage. Since monoubiquitination of FANCD2 is a crucial indicator for cellular response to DNA damage, we monitored the fate of FANCD2 and its monoubiquitination following DNA damage. Disappearance of FANCD2 protein was induced following DNA damage in a dose-dependent manner, which correlated with degradation of BRCA1 and poly-ADP ribose polymerase (PARP), known targets for caspase-mediated apoptosis. Disappearance of FANCD2 was not affected by a proteasome inhibitor but was blocked by a caspase inhibitor. DNA damage-induced disappearance of FANCD2 was also observed in cells lacking FANCA, suggesting that disappearance of FANCD2 does not depend on FANC-BRCA1 pathway and FANCD2 monoubiquitination. In keeping with this, cells treated with TNF-α, an apoptotic stimulus without causing any DNA damage, also induced disappearance of FANCD2 without monoubiquitination. Together, our data suggest that FANCD2 is a target for caspase-mediated apoptotic pathway, which may be an early indicator for apoptotic cell death.

Original languageEnglish
Pages (from-to)2383-2391
Number of pages9
JournalJournal of Cellular Biochemistry
Volume112
Issue number9
DOIs
StatePublished - Sep 2011

Fingerprint

Fanconi Anemia Complementation Group Proteins
Caspases
DNA Damage
DNA
Proteins
Fanconi Anemia Complementation Group D2 Protein
Proteasome Inhibitors
Caspase Inhibitors
Poly(ADP-ribose) Polymerases
Cell death
Cell Death
Apoptosis
Degradation

Keywords

  • Apoptosis
  • Caspase
  • Cisplatin
  • Dna damage
  • DNA repair
  • Fanconi anemia
  • Mitomycin C

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Fanconi anemia D2 protein is an apoptotic target mediated by caspases. / Park, Su Jung; Beck, Brian D.; Saadatzadeh, M. Reza; Haneline, Laura; Clapp, D.; Lee, Suk-Hee.

In: Journal of Cellular Biochemistry, Vol. 112, No. 9, 09.2011, p. 2383-2391.

Research output: Contribution to journalArticle

Park, Su Jung ; Beck, Brian D. ; Saadatzadeh, M. Reza ; Haneline, Laura ; Clapp, D. ; Lee, Suk-Hee. / Fanconi anemia D2 protein is an apoptotic target mediated by caspases. In: Journal of Cellular Biochemistry. 2011 ; Vol. 112, No. 9. pp. 2383-2391.
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