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A new survivin tracer tracks, delocalizes and captures endogenous survivin at different subcellular locations and in distinct organelles

Els Beghein (UGent) , Isabel Van Audenhove (UGent) , Olivier Zwaenepoel (UGent) , Adriaan Verhelle (UGent) , Ariane De Ganck (UGent) and Jan Gettemans (UGent)
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Abstract
Survivin, the smallest member of the inhibitor of apoptosis protein family, plays a central role during mitosis and exerts a cytoprotective function. Survivin is highly expressed in most cancer types and contributes to multiple facets of carcinogenesis. The molecular mechanisms underlying its highly diverse functions need to be extensively explored, which is crucial for rational design of future personalized therapeutics. In this study, we have generated an alpaca survivin nanobody (SVVNb8) that binds with low nanomolar affinity to its target. When expressed as an intrabody in HeLa cells, SVVNb8 faithfully tracks survivin during different phases of mitosis without interfering with survivin function. Furthermore, coupling SVVNb8 with a subcellular delocalization tag efficiently redirects endogenous survivin towards the nucleus, the cytoplasm, peroxisomes and even to the intermembrane space of mitochondria where it presumably interacts with resident mitochondrial survivin. Based on our findings, we believe that SVVNb8 is an excellent instrument to further elucidate survivin biology and topography, and can serve as a model system to investigate mitochondrial and peroxisomal (survivin) protein import.
Keywords
INHIBITS APOPTOSIS, SPINDLE CHECKPOINT, HELA-CELLS, IN-VIVO, PROTEIN, NANOBODIES, CANCER, GENE, COMPLEX, PEROXISOMES

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Chicago
Beghein, Els, Isabel Van Audenhove, Olivier Zwaenepoel, Adriaan Verhelle, Ariane De Ganck, and Jan Gettemans. 2016. “A New Survivin Tracer Tracks, Delocalizes and Captures Endogenous Survivin at Different Subcellular Locations and in Distinct Organelles.” Scientific Reports 6.
APA
Beghein, E., Van Audenhove, I., Zwaenepoel, O., Verhelle, A., De Ganck, A., & Gettemans, J. (2016). A new survivin tracer tracks, delocalizes and captures endogenous survivin at different subcellular locations and in distinct organelles. SCIENTIFIC REPORTS, 6.
Vancouver
1.
Beghein E, Van Audenhove I, Zwaenepoel O, Verhelle A, De Ganck A, Gettemans J. A new survivin tracer tracks, delocalizes and captures endogenous survivin at different subcellular locations and in distinct organelles. SCIENTIFIC REPORTS. 2016;6.
MLA
Beghein, Els, Isabel Van Audenhove, Olivier Zwaenepoel, et al. “A New Survivin Tracer Tracks, Delocalizes and Captures Endogenous Survivin at Different Subcellular Locations and in Distinct Organelles.” SCIENTIFIC REPORTS 6 (2016): n. pag. Print.
@article{8509079,
  abstract     = {Survivin, the smallest member of the inhibitor of apoptosis protein family, plays a central role during mitosis and exerts a cytoprotective function. Survivin is highly expressed in most cancer types and contributes to multiple facets of carcinogenesis. The molecular mechanisms underlying its highly diverse functions need to be extensively explored, which is crucial for rational design of future personalized therapeutics. In this study, we have generated an alpaca survivin nanobody (SVVNb8) that binds with low nanomolar affinity to its target. When expressed as an intrabody in HeLa cells, SVVNb8 faithfully tracks survivin during different phases of mitosis without interfering with survivin function. Furthermore, coupling SVVNb8 with a subcellular delocalization tag efficiently redirects endogenous survivin towards the nucleus, the cytoplasm, peroxisomes and even to the intermembrane space of mitochondria where it presumably interacts with resident mitochondrial survivin. Based on our findings, we believe that SVVNb8 is an excellent instrument to further elucidate survivin biology and topography, and can serve as a model system to investigate mitochondrial and peroxisomal (survivin) protein import.},
  articleno    = {31177},
  author       = {Beghein, Els and Van Audenhove, Isabel and Zwaenepoel, Olivier and Verhelle, Adriaan and De Ganck, Ariane and Gettemans, Jan},
  issn         = {2045-2322},
  journal      = {SCIENTIFIC REPORTS},
  language     = {eng},
  pages        = {16},
  title        = {A new survivin tracer tracks, delocalizes and captures endogenous survivin at different subcellular locations and in distinct organelles},
  url          = {http://dx.doi.org/10.1038/srep31177},
  volume       = {6},
  year         = {2016},
}

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