Towards Structural Studies of Pro-Survival Protein Complexes — ASN Events
  1. Schedule
  2. Session Five - Poster Session A including Refreshments
  3. Towards Structural Studies of Pro-Survival Protein Complexes

Towards Structural Studies of Pro-Survival Protein Complexes (#153)

Maria-Jose Garcia-Bonete 1 , Gergely Katona 1
  1. Goteborg University, Goteborg, GOTEB, Sweden

Survivin is a pro-survival protein implicated in cell survival. It plays a role in apoptosis where acts upstream of effector caspases preventing the Smac/Diablo protein release from the mitochondria which leave X-IAP free to inhibit caspases activation and apoptosis5. In cell cycle regulation, it is also involved and takes part into the Chromosomal Passenger Complex (CPC) which also consists of Aurora kinase B, Borealin and INCENP and participates in spindle formation, kinetochore-microtubule attachments, the spindle checkpoint and cytokinesis1,4.

Survivin is over-expressed in a huge number of cancer (such as central nervous system, lung, melanoma, ovarian, pancreatic, prostate…) and is related to chemotherapy resistance, recurrence and bad outcome.

This 16kDa protein is the smallest member of Inhibitor of Apoptosis Protein family (IAP), it is dimeric in solution, but monomeric survivin can also form protein:protein interactions. In human survivin only a single BIR domain is present (which binds Zn+2 and participates in the inhibition of cell death proteases; caspases)6. An extended carboxyl-terminal α-helix makes survivin also distinct from other IAP proteins6.

We want to identify potential target proteins which interact with survivin in order to understand better its function which could be useful in drug or treatment development. Such diseases are related to survivin deregulation such as cancer, rheumatoid arthritis2… The proteins and peptides to test are expressed in E.coli and are tagged with GFP to identify easily the interaction3. We will characterise the interactions via peptide microarray, microscale thermophoresis and isothermal titration calorimetry. We are also interested in the potential regulatory role of the Zn+2 ion in the BIR domain.  

  1. Altieri D. C. (2003) Survivin, versatile modulation of cell division and apoptosis in cancer. Oncogene, vol. 22
  2. Baran M, Möllers L. N., Anfersson S., Jonsson I., Ekwall A. H., Bjersing J., Tarkowski A. & Bokarewa M. (2009) Survivin is an essential mediator of arthritits interacting with urokinase signalling. Molecular Medicine, vol. 13  
  3. Hsieh J. M., Besserer G. M., Madej M. G., Bui H., Kwon S. & Abramson J. (2010). Bridging the gap: A GFP-based strategy for overexpression and purification of membrane proteins with intra and extracellular C-termini. Protein Science, vol. 19.
  4. Jeyaprakash A. A., Klein R. U., Lindner D., Ebert J., Nigg E. A. & Conti E. (2007) Structure of a Survivin-Borealin-INCENP Core Complex Reveals How Chromosomal Passengers Travel Together. Cell, vol. 131.
  5. Mita A. C., Mita M. M., Nawrocki S. T. & Giles F. J. (2008) Survivin: key regulator of mitosis and apoptosis and novel target for cancer therapeutics. Clinical Cancer Research vol. 15.
  6. Verdecia M. A., Huang H., Dutil E., Kaiser D. A., Hunter T. & Noel J. P. (2000) Structure of the human anti-apoptotic protein survivin reveals a dimeric arrangement. Nature Structure Biology, vol. 7.