The Tumour Specific Pro-Apoptotic Factor Apoptin (Vp3) from Chicken Anaemia Virus

Cristina      Oro; David   A.   Jans

Abstract

Cancer is a growing problem for human health world-wide. Dramatic breakthroughs have increased our understanding of the molecular mechanisms involved in the process of tumorigenesis, allowing us to develop more refined anti-cancer treatments, expanding the repertoire of available anti-cancer drugs, and increasing the efficiency of their delivery to malignant cells. Nevertheless, even with improved understanding of the complex origins of cancer cells, there is a dearth of efficient and above all specific anti-cancer treatments. Apoptin (viral protein 3 - VP3), a gene product derived from the Chicken Anaemia Virus (CAV) represents a novel anti-cancer tool. It appears to have innate tumour-specific p53-independent, Bcl-2-enhanced proapoptotic activity, and hence may be of great utility in the endeavour to achieve specific and efficient elimination of cancer cells, particularly in cases of drug resistance through Bcl-2 overexpression / loss of p53 function etc. This review will examine the unique aspects of apoptins properties, and in particular, its ability to localise specifically in the nucleus of transformed but not normal cells. The latter ability, importantly, appears to be integrally related to its tumour-specific pro-apoptotic action.

Keywords: apoptosis, drug resistance, nuclear targeting signals, nuclear protein import, importins, exportins

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