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.
Chuang
P I
PI
Department of Medicine, University of Washington, Seattle, Washington, USA. ichuang@u.washington.edu
Yee
E
E
Karsan
A
A
Winn
R K
RK
Harlan
J M
JM
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