TY - JOUR
T1 - Yeast two-hybrid screens imply involvement of fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport
AU - Reuter, Tanja Y.
AU - Medhurst, Annette L.
AU - Waisfisz, Quinten
AU - Zhi, Yu
AU - Herterich, Sabine
AU - Hoehn, Holger
AU - Gross, Hans J.
AU - Joenje, Hans
AU - Hoatlin, Maureen E.
AU - Mathew, Christopher G.
AU - Huber, Pia A.J.
N1 - Funding Information:
This work was supported by the Schroeder–Kurth Fonds (Wuerzburg, Germany), MRC (UK), Cancer Research Campaign UK, Leukaemia Research Fund (UK), Dutch Cancer Society (NL), Fanconi Anemia Research Fund (USA), and NIH Grant HL56045 (USA)
PY - 2003/10/1
Y1 - 2003/10/1
N2 - 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.
AB - 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.
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U2 - 10.1016/S0014-4827(03)00261-1
DO - 10.1016/S0014-4827(03)00261-1
M3 - Article
C2 - 14499622
AN - SCOPUS:0141788633
SN - 0014-4827
VL - 289
SP - 211
EP - 221
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 2
ER -