Survivin 2alpha: a novel Survivin splice variant expressed in human malignancies.
BACKGROUND
Survivin and its alternative splice forms are involved in critical cellular processes, including cell division and programmed cell death. Survivin is expressed in the majority of human cancers, but minimally in differentiated normal tissues. Expression levels correlate with tumor aggressiveness and resistance to therapy.


RESULTS
In the present study, we identify and characterize a novel survivin isoform that we designate survivin 2alpha. Structurally, the transcript consists of 2 exons: exon 1 and exon 2, as well as a 3' 197 bp region of intron 2. Acquisition of a new in-frame stop codon within intron 2 results in an open reading frame of 225 nucleotides, predicting a truncated 74 amino acid protein. Survivin 2alpha is expressed at high levels in several malignant cell lines and primary tumors. Functional assays show that survivin 2alpha attenuates the anti-apoptotic activity of survivin. Subcellular localization and immunoprecipitation of survivin 2alpha suggests a physical interaction with survivin.


CONCLUSIONS
We characterized a novel survivin splice variant that we designated survivin 2alpha. We hypothesize that survivin 2alpha can alter the anti-apoptotic functions of survivin in malignant cells. Thus survivin 2alpha may be useful as a therapeutic tool in sensitizing chemoresistant tumor cells to chemotherapy.
Caldas
Hugo
H
Center for Childhood Cancer, Columbus Children's Research Institute Columbus, OH, USA. caldash@ccri.net <caldash@ccri.net>
Honsey
Laura E
LE
Altura
Rachel A
RA
D017398:Alternative Splicing / Q000235:genetics*; D017209:Apoptosis; D001483:Base Sequence; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D040681:Structural Homology, Protein; D000077022:Survivin
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D000077022:Survivin
J Clin Invest. 2004 Oct;114(8):1117-27
15489959
Oncogene. 2004 Sep 30;23(45):7545-51
15334064
Biochem Biophys Res Commun. 2004 Feb 13;314(3):902-7
14741722
Br J Cancer. 2003 Nov 3;89(9):1743-9
14583779
Cancer Res. 2003 Sep 15;63(18):5703-6
14522887
J Cell Sci. 2003 Jul 15;116(Pt 14):2987-98
12783991
Oncogene. 1998 Dec 24;17(25):3247-59
9916987
J Cell Sci. 2003 May 1;116(Pt 9):1653-8
12665546
Blood. 2002 Oct 1;100(7):2463-71
12239157
Gastroenterology. 2002 Aug;123(2):619-31
12145814
J Cell Biol. 2000 Dec 25;151(7):1575-82
11134084
Curr Biol. 2000 Nov 2;10(21):1319-28
11084331
Mol Cell. 2000 Jul;6(1):173-82
10949038
Blood. 2000 Feb 15;95(4):1435-42
10666222
Cancer Res. 1999 Dec 15;59(24):6097-102
10626797
Lancet. 1998 Mar 21;351(9106):882-3
9525374
Nat Med. 1997 Aug;3(8):917-21
9256286
Am J Pathol. 1998 Jan;152(1):43-9
9422522
J Biol Chem. 1998 May 1;273(18):11177-82
9556606
Gene. 1996 Sep 26;174(1):115-20
8863737