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 language | English (US) |
|---|---|
| Pages (from-to) | 2383-2391 |
| Number of pages | 9 |
| Journal | Journal of Cellular Biochemistry |
| Volume | 112 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 1 2011 |
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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 journal › Article
}
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 -