Fanconi anemia D2 protein is an apoptotic target mediated by caspases

Su Jung Park, Brian D. Beck, M. Reza Saadatzadeh, Laura S. Haneline, D. Wade 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 (US)
Pages (from-to)2383-2391
Number of pages9
JournalJournal of Cellular Biochemistry
Volume112
Issue number9
DOIs
StatePublished - Sep 1 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 S.; Clapp, D. Wade; Lee, Suk Hee.

In: Journal of Cellular Biochemistry, Vol. 112, No. 9, 01.09.2011, p. 2383-2391.

Research output: Contribution to journalArticle

Park, Su Jung ; Beck, Brian D. ; Saadatzadeh, M. Reza ; Haneline, Laura S. ; Clapp, D. Wade ; 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.
@article{ff26590cea18479684201f39eba46765,
title = "Fanconi anemia D2 protein is an apoptotic target mediated by caspases",
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.",
keywords = "Apoptosis, Caspase, Cisplatin, Dna damage, DNA repair, Fanconi anemia, Mitomycin C",
author = "Park, {Su Jung} and Beck, {Brian D.} and Saadatzadeh, {M. Reza} and Haneline, {Laura S.} and Clapp, {D. Wade} and Lee, {Suk Hee}",
year = "2011",
month = "9",
day = "1",
doi = "10.1002/jcb.23161",
language = "English (US)",
volume = "112",
pages = "2383--2391",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "9",

}

TY - JOUR

T1 - Fanconi anemia D2 protein is an apoptotic target mediated by caspases

AU - Park, Su Jung

AU - Beck, Brian D.

AU - Saadatzadeh, M. Reza

AU - Haneline, Laura S.

AU - Clapp, D. Wade

AU - Lee, Suk Hee

PY - 2011/9/1

Y1 - 2011/9/1

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Caspase

KW - Cisplatin

KW - Dna damage

KW - DNA repair

KW - Fanconi anemia

KW - Mitomycin C

UR - http://www.scopus.com/inward/record.url?scp=84860404194&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860404194&partnerID=8YFLogxK

U2 - 10.1002/jcb.23161

DO - 10.1002/jcb.23161

M3 - Article

C2 - 21520247

AN - SCOPUS:84860404194

VL - 112

SP - 2383

EP - 2391

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 9

ER -