Poriferan survivin exhibits a conserved regulatory role in the interconnected pathways of cell cycle and apoptosis

Matthias Wiens (1) , Bérengère Luthringer (1) , Simone Isbert (1) , Werner E.G. Müller (1) , Carla Zilberberg (1) , Narsinh L. Thakur (1) , Gert Wörheide (1) , Roland H. Stauber (1) , Merike Kelve (1)

1 Institute for Physiological Chemistry and Pathobiochemistry

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 anti-apoptotic 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 shares considerable similarities with its metazoan homologues, ranging from conserved exon/intron structure to presence of protein-interaction domains. Whereas sponge tissue displays a low steady-state level, SURVL expression was significantly up-regulated 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.

Mots clés: survivin; IAP; caspase; sponges; Suberites domuncula

Matthias Wiens, Bérengère Luthringer, Simone Isbert, Werner E.G. Müller, Carla Zilberberg, et al.. Poriferan survivin exhibits a conserved regulatory role in the interconnected pathways of cell cycle and apoptosis. Cell Death and Differentiation, 2010, ⟨10.1038/cdd.2010.87⟩. ⟨hal-00558637⟩