A1 is a constitutive and inducible Bcl-2 homologue in mature human neutrophils.
During the process of terminal differentiation toward mature neutrophils, the anti-apoptotic proteins Bcl-2 and Bcl-x become down-regulated and eventually cease to be expressed, whereas the death-promoting Bcl-2 homologue, Bax, persists. Thus, the disappearance of anti-apoptotic homologues was thought to account for the early demise of mature neutrophils. However, although the survival of mature human neutrophils can be prolonged by a variety of factors, no anti-apoptotic Bcl-2 homologues have previously been identified. Human A1 is a Bcl-2 homologue previously shown to be present in endothelial cells and to convey anti-apoptotic function in vitro. We describe here that human A1 mRNA is constitutively expressed in mature neutrophils and is up-regulated by G-CSF and LPS, agonists that promote neutrophil survival. In addition, we show progressive A1 mRNA accumulation in HL-60 cells during all-trans retinoic acid-driven neutrophilic differentiation. Our findings suggest that A1 may have an important role in neutrophilic development and in modulating mature neutrophil survival.
Department of Medicine, University of Washington, Seattle, Washington, USA. ichuang@u.washington.edu
P I
PI
Chuang
E
E
Yee
A
A
Karsan
R K
RK
Winn
J M
JM
Harlan
D017209:Apoptosis; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000097:blood* / Q000235:genetics; D005786:Gene Expression Regulation; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D018922:HL-60 Cells / Q000378:metabolism; D018398:Homeodomain Proteins; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D015778:Minor Histocompatibility Antigens; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D009504:Neutrophils / Q000737:chemistry*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000097:blood*; D012333:RNA, Messenger / Q000097:blood / Q000378:metabolism; D051818:Replication Protein C; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014212:Tretinoin / Q000494:pharmacology
C096816:BCL2-related protein A1; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D008070:Lipopolysaccharides; C096063:MATA1 protein, S cerevisiae; D015778:Minor Histocompatibility Antigens; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D016179:Granulocyte Colony-Stimulating Factor; D014212:Tretinoin; D051818:Replication Protein C