Fanconi anemia group C protein prevents apoptosis in hematopoietic cells through redox regulation of GSTP1 - PubMed

Fanconi anemia group C protein prevents apoptosis in hematopoietic cells through redox regulation of GSTP1

R C Cumming et al. Nat Med. 2001 Jul.

Abstract

The Fanconi anemia group C protein (FANCC) plays an important role in hematopoiesis by ensuring the survival of hematopoietic progenitor cells through an unknown mechanism. We investigated the function of FANCC by identifying FANCC-binding proteins in hematopoietic cells. Here we show that glutathione S-transferase P1-1 (GSTP1) interacts with FANCC, and that overexpression of both proteins in a myeloid progenitor cell line prevents apoptosis following factor deprivation. FANCC increases GSTP1 activity after the induction of apoptosis. GSTP1 is an enzyme that catalyzes the detoxification of xenobiotics and by-products of oxidative stress, and it is frequently upregulated in neoplastic cells. Although FANCC lacks homology with conventional disulfide reductases, it functions by preventing the formation of inactivating disulfide bonds within GSTP1 during apoptosis. The prevention of protein oxidation by FANCC reveals a novel mechanism of enzyme regulation during apoptosis and has implications for the treatment of degenerative diseases with thiol reducing agents.

Comment in

• Cellular function of the Fanconi anemia pathway.

  D'Andrea AD. D'Andrea AD. Nat Med. 2001 Dec;7(12):1259-60. doi: 10.1038/nm1201-1259a. Nat Med. 2001. PMID: 11726938 No abstract available.

Similar articles

• Hematopoietic stem cells from fancc(-/-) mice have lower growth and differentiation potential in response to growth factors.

  Aubé M, Lafrance M, Charbonneau C, Goulet I, Carreau M. Aubé M, et al. Stem Cells. 2002;20(5):438-47. doi: 10.1634/stemcells.20-5-438. Stem Cells. 2002. PMID: 12351814

• Fanconi anaemia proteins: major roles in cell protection against oxidative damage.

  Pagano G, Youssoufian H. Pagano G, et al. Bioessays. 2003 Jun;25(6):589-95. doi: 10.1002/bies.10283. Bioessays. 2003. PMID: 12766948 Review.

• Cellular function of the Fanconi anemia pathway.

  D'Andrea AD. D'Andrea AD. Nat Med. 2001 Dec;7(12):1259-60. doi: 10.1038/nm1201-1259a. Nat Med. 2001. PMID: 11726938 No abstract available.

• Expression of the Fanconi anemia group C gene in hematopoietic cells is not influenced by oxidative stress, cross-linking agents, radiation, heat, or mitotic inhibitory factors.

  Tower PA, Christianson TA, Peters ST, Ostroski ML, Hoatlin ME, Zigler AJ, Heinrich MC, Rathbun RK, Keeble W, Faulkner GR, Bagby GC Jr. Tower PA, et al. Exp Hematol. 1998 Jan;26(1):19-26. Exp Hematol. 1998. PMID: 9430510

• Molecular biology of Fanconi anaemia--an old problem, a new insight.

  Ahmad SI, Hanaoka F, Kirk SH. Ahmad SI, et al. Bioessays. 2002 May;24(5):439-48. doi: 10.1002/bies.10082. Bioessays. 2002. PMID: 12001267 Review.

Cited by

• Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp.

  Alfarouk KO, Stock CM, Taylor S, Walsh M, Muddathir AK, Verduzco D, Bashir AH, Mohammed OY, Elhassan GO, Harguindey S, Reshkin SJ, Ibrahim ME, Rauch C. Alfarouk KO, et al. Cancer Cell Int. 2015 Jul 15;15:71. doi: 10.1186/s12935-015-0221-1. eCollection 2015. Cancer Cell Int. 2015. PMID: 26180516 Free PMC article.

• Mitoprotective Clinical Strategies in Type 2 Diabetes and Fanconi Anemia Patients: Suggestions for Clinical Management of Mitochondrial Dysfunction.

  Pagano G, Pallardó FV, Porto B, Fittipaldi MR, Lyakhovich A, Trifuoggi M. Pagano G, et al. Antioxidants (Basel). 2020 Jan 18;9(1):82. doi: 10.3390/antiox9010082. Antioxidants (Basel). 2020. PMID: 31963742 Free PMC article. Review.

• Fanconi anemia signaling and Mus81 cooperate to safeguard development and crosslink repair.

  Larin M, Gallo D, Tamblyn L, Yang J, Liao H, Sabat N, Brown GW, McPherson JP. Larin M, et al. Nucleic Acids Res. 2014 Sep;42(15):9807-20. doi: 10.1093/nar/gku676. Epub 2014 Jul 23. Nucleic Acids Res. 2014. PMID: 25056314 Free PMC article.

• Inflammatory reactive oxygen species-mediated hemopoietic suppression in Fancc-deficient mice.

  Sejas DP, Rani R, Qiu Y, Zhang X, Fagerlie SR, Nakano H, Williams DA, Pang Q. Sejas DP, et al. J Immunol. 2007 Apr 15;178(8):5277-87. doi: 10.4049/jimmunol.178.8.5277. J Immunol. 2007. PMID: 17404312 Free PMC article.

• Molecular pathogenesis of fanconi anemia.

  Taniguchi T, Dandrea AD. Taniguchi T, et al. Int J Hematol. 2002 Feb;75(2):123-8. doi: 10.1007/BF02982016. Int J Hematol. 2002. PMID: 11939257 Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Nature Publishing Group

• Other Literature Sources

  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal