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A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF.

Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome. The phenotype includes developmental defects, bone marrow failure, and cell cycle abnormalities. At least eight complementation groups (A-H) exist, and although three of the corresponding complementation group genes have been cloned, they lack recognizable motifs, and their functions are unknown. We have isolated a binding partner for the Fanconi anemia group C protein (FANCC) by yeast two-hybrid screening. We show that the novel gene, FAZF, encodes a 486 amino acid protein containing a conserved amino terminal BTB/POZ protein interaction domain and three C-terminal Kr├╝ppel-like zinc fingers. FAZF is homologous to the promyelocytic leukemia zinc finger (PLZF) protein, which has been shown to act as a transcriptional repressor by recruitment of nuclear corepressors (N-CoR, Sin3, and HDAC1 complex). Consistent with a role in FA, BTB/POZ-containing proteins have been implicated in oncogenesis, limb morphogenesis, hematopoiesis, and proliferation. We show that FAZF is a transcriptional repressor that is able to bind to the same DNA target sequences as PLZF. Our data suggest that the FAZF/FANCC interaction maps to a region of FANCC deleted in FA patients with a severe disease phenotype. We also show that FAZF and wild-type FANCC can colocalize in nuclear foci, whereas a patient-derived mutant FANCC that is compromised for nuclear localization cannot. These results suggest that the function of FANCC may be linked to a transcriptional repression pathway involved in chromatin remodeling.

Pubmed ID: 10572087


  • Hoatlin ME
  • Zhi Y
  • Ball H
  • Silvey K
  • Melnick A
  • Stone S
  • Arai S
  • Hawe N
  • Owen G
  • Zelent A
  • Licht JD



Publication Data

December 1, 1999

Associated Grants

  • Agency: NCI NIH HHS, Id: CA59938
  • Agency: NHLBI NIH HHS, Id: HL56045
  • Agency: NCI NIH HHS, Id: K08 CA73762

Mesh Terms

  • Amino Acid Sequence
  • Base Sequence
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Fanconi Anemia
  • Fanconi Anemia Complementation Group C Protein
  • Fanconi Anemia Complementation Group Proteins
  • Gene Expression Regulation
  • Humans
  • Kruppel-Like Transcription Factors
  • Molecular Sequence Data
  • Nuclear Proteins
  • Proteins
  • Repressor Proteins
  • Transcription Factors