Nuclear survivin has reduced stability and is not cytoprotective.
Survivin is an essential mitotic protein that is overexpressed in many cancers, and its presence is correlated with increased resistance to radiation and chemotherapy. Here we demonstrate that sending survivin into the nucleus accelerates its degradation in a cdh1-dependent manner, abolishes the radio resistance normally conferred to cells by its overexpression, and prevents survivin from inhibiting apoptosis without affecting its mitotic localization. Our data suggest that targeting survivin to the nucleus provides an efficient means of eliminating it from the cell and may prove a novel strategy in cancer treatment, particularly in combination with radiotherapy.
Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ, United Kingdom.
Claire M
CM
Connell
Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ, United Kingdom.
Rita
R
Colnaghi
Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ, United Kingdom. Electronic address: s.p.wheatley@sussex.ac.uk.
Sally P
SP
Wheatley
D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000502:physiology*; D008938:Mitosis; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D019913:Nuclear Localization Signals; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013347:Subcellular Fractions / Q000378:metabolism; D000077022:Survivin; D013997:Time Factors
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D019913:Nuclear Localization Signals; D000077022:Survivin; D049452:Green Fluorescent Proteins