The effects of the Fanconi anemia zinc finger (FAZF) on cell cycle, apoptosis, and proliferation are differentiation stage-specific.
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 G(1) 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.
Dai
Mu-Shui
MS
Division of Molecular Medicine, Oregon Health and Science University, Portland, Oregon 97201, USA.
Chevallier
Nathalie
N
Stone
Stacie
S
Heinrich
Michael C
MC
McConnell
Melanie
M
Reuter
Tanja
T
Broxmeyer
Hal E
HE
Licht
Jonathan D
JD
Lu
Li
L
Hoatlin
Maureen E
ME
D018952:Antigens, CD34 / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000502:physiology*; D016193:G1 Phase; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D009842:Oligopeptides; D010455:Peptides; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016335:Zinc Fingers / Q000502:physiology*
D018952:Antigens, CD34; D004268:DNA-Binding Proteins; D009842:Oligopeptides; D010455:Peptides; D012097:Repressor Proteins; C498646:ZBTB32 protein, human; C085706:FLAG peptide