Survivin increased vascular development during Xenopus ontogenesis.
Survivin is a member of the inhibitor of apoptosis proteins (IAP) family. These proteins contain one to three zinc-binding motifs termed bacculoviral IAP-binding repeats (BIRs). Survivin contains a single BIR motif. Contrary to other members that directly interact with caspases and inhibit apoptosis, Survivin is believed to have both antiapoptotic and proliferative functions. In mammals, Survivin is not detected in most adult tissues except in endothelial cells of newly formed capillaries and large blood vessels. Importantly, Survivin is highly expressed in all common human cancers. To gain a better view of Survivin expression and function during development, we used the amphibian Xenopus developmental model. We show that the genomes of X. laevis, X. tropicalis, Zebrafish, fugu pufferfish, and rainbow trout encode two different Survivin genes (Su1 and Su2), contrary to mammalian genomes, which encode a single one. In X. laevis, these two genes have a differential spatiotemporal transcription pattern. Transgenic expression of Su1 leads to an enlargement of tadpole's blood vessels with an increase in the number of endothelial cells. This effect requires a functional BIR domain and the p34/cdc2 phosphorylation site. It does not seem to rely on the antiapoptotic activity of Su1 as it is not observed in tadpoles overexpressing other antiapoptotic factors such as XIAP or BclXL. We conclude that Su1 ubiquitous gain of function leads directly or indirectly to an increase in blood vessels size via the proliferation of endothelial cells.
Du Pasquier
David
D
Laboratoire de Transgenèse et Génétique des Amphibiens, UMR-8080, IBAIC, Université Paris-Sud, 91405 Orsay, France.
Phung
Albert Chesneau
AC
Ymlahi-Ouazzani
Qods
Q
Sinzelle
Ludivine
L
Ballagny
Chantal
C
Bronchain
Odile
O
Du Pasquier
Louis
L
Mazabraud
André
A
D000595:Amino Acid Sequence; D000818:Animals; D001808:Blood Vessels / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D006801:Humans; D017403:In Situ Hybridization; D051034:Inhibitor of Apoptosis Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014981:Xenopus
D051034:Inhibitor of Apoptosis Proteins