Phosphorylation of survivin at threonine 34 inhibits its mitotic function and enhances its cytoprotective activity.
Survivin is an essential chromosomal passenger protein required for mitotic progression. It is also an inhibitor of apoptosis and can prevent caspase-mediated cell death. In addition, survivin levels are elevated in cancer cells where its presence correlates with increased resistance to chemo- and radio-therapy, which makes it an attractive target for novel anti-cancer strategies. Interestingly, survivin is phosphorylated by the mitotic kinase, cdk1, and a nonphosphorylatable form, survivin(T34A), cannot inhibit apoptosis. Here we rigorously test the ability of survivin(T34A) and its corresponding phosphomimetic, survivin(T34E), to promote cell viability through survivin's dual roles. The effects of these mutations are diametrically opposed: survivin(T34A) accelerates cell proliferation and promotes apoptosis, whereas survivin(T34E) retards growth and promotes survival. Thus the phosphorylation status of survivin at T34 is pivotal to a cell's decision to live or die.
Barrett
Rachel M A
RM
Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton, UK.
Osborne
Toby P
TP
Wheatley
Sally P
SP
D016203:CDC2 Protein Kinase / Q000378:metabolism; D016923:Cell Death; D049109:Cell Proliferation; D019610:Cytoprotection; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D008938:Mitosis; D009154:Mutation; D010766:Phosphorylation; D013912:Threonine / Q000235:genetics / Q000378:metabolism*
D008869:Microtubule-Associated Proteins; D049452:Green Fluorescent Proteins; D013912:Threonine; D016203:CDC2 Protein Kinase