The effects of the Fanconi anemia zinc finger (FAZF) on cell cycle, apoptosis, and proliferation are differentiation stage-specific

Mu Shui Dai, Nathalie Chevallier, Stacie Stone, Michael C. Heinrich, Melanie McConnell, Tanja Reuter, Hal E. Broxmeyer, Jonathan D. Licht, Li Lu, Maureen E. Hoatlin

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Abstract

FAZF, a member of the BTB/POZ family of transcriptional repressor proteins, has been shown to bind to FANCC, the protein defective in patients with the bone marrow failure syndrome Fanconi anemia complementation group C. Because bone marrow failure in Fanconi anemia has been attributed to a failure of the hematopoietic stem cell population to produce sufficient progeny, we documented the expression of FAZF in human CD34+ hematopoietic progenitor cells. FAZF was expressed at high levels in early stages of differentiation but declined during subsequent differentiation into erythroid and myeloid lineages. Consistent with its presumed role as a transcriptional repressor, FAZF was found in the nuclear compartment, where it resides in distinct nuclear speckles at or near sites of DNA replication. Using a FAZF-inducible myeloid cell line, we found that enforced expression of FAZF was accompanied by accumulation in the G1 phase of the cell cycle followed later by apoptosis. These results suggest an essential role for FAZF during the proliferative stages of primitive hematopoietic progenitors, possibly acting in concert with (a subset of) the Fanconi anemia proteins.

Original languageEnglish (US)
Pages (from-to)26327-26334
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number29
DOIs
StatePublished - Jul 19 2002

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Dai, M. S., Chevallier, N., Stone, S., Heinrich, M. C., McConnell, M., Reuter, T., Broxmeyer, H. E., Licht, J. D., Lu, L., & Hoatlin, M. E. (2002). The effects of the Fanconi anemia zinc finger (FAZF) on cell cycle, apoptosis, and proliferation are differentiation stage-specific. Journal of Biological Chemistry, 277(29), 26327-26334. https://doi.org/10.1074/jbc.M201834200