Yeast two-hybrid screens imply involvement of fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport

Tanja Y. Reuter, Annette L. Medhurst, Quinten Waisfisz, Yu Zhi, Sabine Herterich, Holger Hoehn, Hans J. Gross, Hans Joenje, Maureen Hoatlin, Christopher G. Mathew, Pia A J Huber

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Abstract

Mutations in one of at least eight different genes cause bone marrow failure, chromosome instability, and predisposition to cancer associated with the rare genetic syndrome Fanconi anemia (FA). The cloning of seven genes has provided the tools to study the molecular pathway disrupted in Fanconi anemia patients. The structure of the genes and their gene products provided few clues to their functional role. We report here the use of 3 FA proteins, FANCA, FANCC, and FANCG, as "baits" in the hunt for interactors to obtain clues for FA protein functions. Using five different human cDNA libraries we screened 36.5 × 106 clones with the technique of the yeast two-hybrid system. We identified 69 proteins which have not previously been linked to the FA pathway as direct interactors of FANCA, FANCC, or FANCG. Most of these proteins are associated with four functional classes including transcription regulation (21 proteins), signaling (13 proteins), oxidative metabolism (10 proteins), and intracellular transport (11 proteins). Interaction with 6 proteins, DAXX, Ran, IκBγ, USP14, and the previously reported SNX5 and FAZF, was additionally confirmed by coimmunoprecipitation and/or colocalization studies. Taken together, our data strongly support the hypothesis that FA proteins are functionally involved in several complex cellular pathways including transcription regulation, cell signaling, oxidative metabolism, and cellular transport.

Original languageEnglish (US)
Pages (from-to)211-221
Number of pages11
JournalExperimental Cell Research
Volume289
Issue number2
DOIs
StatePublished - Oct 1 2003

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Fanconi Anemia Complementation Group Proteins
Fanconi Anemia
Yeasts
Genes
Proteins
ran GTP-Binding Protein
Chromosomal Instability
Two-Hybrid System Techniques
Protein Transport
Gene Library
Organism Cloning
Clone Cells
Bone Marrow
Mutation
Neoplasms

ASJC Scopus subject areas

  • Cell Biology

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Yeast two-hybrid screens imply involvement of fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport. / Reuter, Tanja Y.; Medhurst, Annette L.; Waisfisz, Quinten; Zhi, Yu; Herterich, Sabine; Hoehn, Holger; Gross, Hans J.; Joenje, Hans; Hoatlin, Maureen; Mathew, Christopher G.; Huber, Pia A J.

In: Experimental Cell Research, Vol. 289, No. 2, 01.10.2003, p. 211-221.

Research output: Contribution to journalArticle

Reuter, Tanja Y. ; Medhurst, Annette L. ; Waisfisz, Quinten ; Zhi, Yu ; Herterich, Sabine ; Hoehn, Holger ; Gross, Hans J. ; Joenje, Hans ; Hoatlin, Maureen ; Mathew, Christopher G. ; Huber, Pia A J. / Yeast two-hybrid screens imply involvement of fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport. In: Experimental Cell Research. 2003 ; Vol. 289, No. 2. pp. 211-221.
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