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Convergence of the fanconi anemia and ataxia telangiectasia signaling pathways.

Publication ,  Journal Article
Taniguchi, T; Garcia-Higuera, I; Xu, B; Andreassen, PR; Gregory, RC; Kim, S-T; Lane, WS; Kastan, MB; D'Andrea, AD
Published in: Cell
May 17, 2002
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Fanconi anemia (FA) and ataxia telangiectasia (AT) are clinically distinct autosomal recessive disorders characterized by spontaneous chromosome breakage and hematological cancers. FA cells are hypersensitive to mitomycin C (MMC), while AT cells are hypersensitive to ionizing radiation (IR). Here, we identify the Fanconi anemia protein, FANCD2, as a link between the FA and ATM damage response pathways. ATM phosphorylates FANCD2 on serine 222 in vitro. This site is also phosphorylated in vivo in an ATM-dependent manner following IR. Phosphorylation of FANCD2 is required for activation of an S phase checkpoint. The ATM-dependent phosphorylation of FANCD2 on S222 and the FA pathway-dependent monoubiquitination of FANCD2 on K561 are independent posttranslational modifications regulating discrete cellular signaling pathways. Biallelic disruption of FANCD2 results in both MMC and IR hypersensitivity.

Duke Scholars

Michael Barry Kastan
Author Michael Barry Kastan Pharmacology & Cancer Biology
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Published In

Cell

DOI

10.1016/s0092-8674(02)00747-x

ISSN

0092-8674

Publication Date

May 17, 2002

Volume

109

Issue

4

Start / End Page

459 / 472

Location

United States

Related Subject Headings

  • Ubiquitin
  • Tumor Suppressor Proteins
  • Signal Transduction
  • S Phase
  • Radiation, Ionizing
  • Protein Serine-Threonine Kinases
  • Phosphoserine
  • Phosphorylation
  • Nucleic Acid Synthesis Inhibitors
  • Nuclear Proteins
 

Citation

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Taniguchi, T., Garcia-Higuera, I., Xu, B., Andreassen, P. R., Gregory, R. C., Kim, S.-T., … D’Andrea, A. D. (2002). Convergence of the fanconi anemia and ataxia telangiectasia signaling pathways. Cell, 109(4), 459–472. https://doi.org/10.1016/s0092-8674(02)00747-x
Taniguchi, Toshiyasu, Irene Garcia-Higuera, Bo Xu, Paul R. Andreassen, Richard C. Gregory, Seong-Tae Kim, William S. Lane, Michael B. Kastan, and Alan D. D’Andrea. “Convergence of the fanconi anemia and ataxia telangiectasia signaling pathways.” Cell 109, no. 4 (May 17, 2002): 459–72. https://doi.org/10.1016/s0092-8674(02)00747-x.
Taniguchi T, Garcia-Higuera I, Xu B, Andreassen PR, Gregory RC, Kim S-T, et al. Convergence of the fanconi anemia and ataxia telangiectasia signaling pathways. Cell. 2002 May 17;109(4):459–72.
Taniguchi, Toshiyasu, et al. “Convergence of the fanconi anemia and ataxia telangiectasia signaling pathways.” Cell, vol. 109, no. 4, May 2002, pp. 459–72. Pubmed, doi:10.1016/s0092-8674(02)00747-x.
Taniguchi T, Garcia-Higuera I, Xu B, Andreassen PR, Gregory RC, Kim S-T, Lane WS, Kastan MB, D’Andrea AD. Convergence of the fanconi anemia and ataxia telangiectasia signaling pathways. Cell. 2002 May 17;109(4):459–472.
Journal cover image

Published In

Cell

DOI

10.1016/s0092-8674(02)00747-x

ISSN

0092-8674

Publication Date

May 17, 2002

Volume

109

Issue

4

Start / End Page

459 / 472

Location

United States

Related Subject Headings

  • Ubiquitin
  • Tumor Suppressor Proteins
  • Signal Transduction
  • S Phase
  • Radiation, Ionizing
  • Protein Serine-Threonine Kinases
  • Phosphoserine
  • Phosphorylation
  • Nucleic Acid Synthesis Inhibitors
  • Nuclear Proteins