Poriferan survivin exhibits a conserved regulatory role in the interconnected pathways of cell cycle and apoptosis.
Survivin orchestrates intracellular pathways during cell division and apoptosis. Its central function as mitotic regulator and inhibitor of cell death has major implications for tumor cell proliferation. Analyses in early-branching Metazoa so far propose an exclusive role of survivin as a chromosomal passenger protein, whereas only later during evolution a complementary antiapoptotic function might have arisen, concurrent with increased organismal complexity. To lift the veil on the ancestral function(s) of this key regulator, a survivin-like protein (SURVL) of one of the earliest-branching metazoan taxa was identified and functionally characterized. SURVL of the sponge Suberites domuncula shares considerable similarities with its metazoan homologs, ranging from conserved exon/intron structure to presence of protein-interaction domains. Whereas sponge tissue shows a low steady-state level, SURVL expression was significantly upregulated in rapidly proliferating primmorph cells. In addition, challenge of tissue and primmorphs with heavy metal or lipopeptide stimulated SURVL expression, concurrent with the expression of a newly discovered caspase. Complementary functional analyses in transfected HEK-293 cells revealed that heterologous expression of a SURVL-EFGP fusion not only promotes proliferation but also enhances resistance to cadmium-induced cell death. Taken together, these results suggest both a deep evolutionary conserved dual role of survivin and an equally conserved central position in the interconnected pathways of cell cycle and apoptosis.
Luthringer
B
B
Institute for Physiological Chemistry and Pathobiochemistry, Johannes Gutenberg University, Medical School, Duesbergweg 6, Mainz, Germany.
Isbert
S
S
Müller
W E G
WE
Zilberberg
C
C
Thakur
N L
NL
Wörheide
G
G
Stauber
R H
RH
Kelve
M
M
Wiens
M
M
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002104:Cadmium / Q000633:toxicity; D020169:Caspases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D002455:Cell Division; D002460:Cell Line; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D055666:Lipopeptides / Q000494:pharmacology; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D047233:Suberites / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D051034:Inhibitor of Apoptosis Proteins; D055666:Lipopeptides; D011993:Recombinant Fusion Proteins; D002104:Cadmium; D020169:Caspases