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

Maureen Hoatlin, Zhi Yu, Helen Ball, Kirsten Silvey, Ari Melnick, Stacie Stone, Sally Arai, Nicola Hawe, Gareth Owen, Arthur Zelent, Jonathan D. Licht

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

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 Kruppel-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.

Original languageEnglish (US)
Pages (from-to)3737-3747
Number of pages11
JournalBlood
Volume94
Issue number11
StatePublished - Dec 1 1999

Fingerprint

Fanconi Anemia Complementation Group C Protein
Repressor Proteins
Fanconi Anemia
Zinc Fingers
Zinc
Leukemia
Genes
Protein Interaction Domains and Motifs
Phenotype
Co-Repressor Proteins
Proteins
Chromatin Assembly and Disassembly
Hematopoiesis
Morphogenesis
Bone Marrow Cells
Yeast
Chromatin
Cell Cycle
Screening
Bone

ASJC Scopus subject areas

  • Hematology

Cite this

Hoatlin, M., Yu, Z., Ball, H., Silvey, K., Melnick, A., Stone, S., ... Licht, J. D. (1999). A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF. Blood, 94(11), 3737-3747.

A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF. / Hoatlin, Maureen; Yu, Zhi; Ball, Helen; Silvey, Kirsten; Melnick, Ari; Stone, Stacie; Arai, Sally; Hawe, Nicola; Owen, Gareth; Zelent, Arthur; Licht, Jonathan D.

In: Blood, Vol. 94, No. 11, 01.12.1999, p. 3737-3747.

Research output: Contribution to journalArticle

Hoatlin, M, Yu, Z, Ball, H, Silvey, K, Melnick, A, Stone, S, Arai, S, Hawe, N, Owen, G, Zelent, A & Licht, JD 1999, 'A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF', Blood, vol. 94, no. 11, pp. 3737-3747.
Hoatlin M, Yu Z, Ball H, Silvey K, Melnick A, Stone S et al. A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF. Blood. 1999 Dec 1;94(11):3737-3747.
Hoatlin, Maureen ; Yu, Zhi ; Ball, Helen ; Silvey, Kirsten ; Melnick, Ari ; Stone, Stacie ; Arai, Sally ; Hawe, Nicola ; Owen, Gareth ; Zelent, Arthur ; Licht, Jonathan D. / A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF. In: Blood. 1999 ; Vol. 94, No. 11. pp. 3737-3747.
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