Bfl-1S, a novel alternative splice variant of Bfl-1, localizes in the nucleus via its C-terminus and prevents cell death.
Bfl-1 is an antiapoptotic Bcl-2 family member and a mouse A1 homologue. The mouse A1 has been reported to have three isoforms, but little is known about human Bfl-1. By reverse-transcriptase polymerase chain reaction analysis, we have identified Bfl-1S (short form), an alternative splice variant of Bfl-1. The Bfl-1S primary sequence contains four conserved Bcl-2 homology (BH) domains and a positive-charged C-terminus containing KKRK amino acids. The expression of Bfl-1S mRNA was detected predominantly in normal lymph nodes and in B-lymphoid leukemia cells. Confocal microscopic analysis using green fluorescence protein fusion proteins demonstrated that Bfl-1S is localized in the nucleus by its C-terminus as an intrinsic nuclear localization sequence. Bfl-1S acts as an antiapoptotic agent in coexpression experiments with Bax, a proapoptotic molecule. The expression of Bfl-1S provided significant resistance against staurosporine (STS) treatments in Molt-4 human T-leukemia cells. Bfl-1S also significantly inhibited the cleavage of Bid, and of caspases 3 and 8 against STS treatment. These results indicate that Bfl-1S is a novel human Bcl-2 family member that possesses antiapoptotic function.
Ko
Jae-Kyun
JK
Department of Pathology, Tumor Immunity Medical Research Center and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Lee
Min-Jung
MJ
Cho
Sun-Hee
SH
Cho
Jung-Ah
JA
Lee
Bo-Young
BY
Koh
Jason Soonju
JS
Lee
Seung-Sook
SS
Shim
Yhong-Hee
YH
Kim
Chul-Woo
CW
D017398:Alternative Splicing; D017209:Apoptosis / Q000235:genetics; D051023:BH3 Interacting Domain Death Agonist Protein; D002352:Carrier Proteins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D015458:Leukemia, T-Cell / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D015778:Minor Histocompatibility Antigens; D008928:Mitochondria / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism
C096816:BCL2-related protein A1; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D002352:Carrier Proteins; D015778:Minor Histocompatibility Antigens; D020033:Protein Isoforms; D019253:Proto-Oncogene Proteins c-bcl-2; D020169:Caspases