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

Blood | Dec 1, 1999

http://www.ncbi.nlm.nih.gov/pubmed/10572087

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 Krüppel-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 RIS Download

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

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Associated grants

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

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