Apoptin: specific killer of tumor cells?
In the early 1990s it was discovered that the VP3/Apoptin protein encoded by the Chicken Anemia virus (CAV) possesses an inherent ability to specifically kill cancer cells. Apoptin was found to be located in the cytoplasm of normal cells while in tumor cells it was localized mainly in the nucleus.(1) These differences in the localization pattern were suggested to be the main mechanism by which normal cells show resistance to Apoptin-mediated cell killing. Although the mechanism of action of Apoptin is presently unknown, it seems to function by the induction of programmed cell death (PCD) after translocation from the cytoplasm to the nucleus and arresting the cell cycle at G2/M, possibly by interfering with the cyclosome.(2) In addition, cancer specific phosphorylation of Threonine residue 108 has been suggested to be important for Apoptin's function to kill tumor cells.(3) In contrast to the large number of publications reporting that nuclear localization, induction of PCD and phosphorylation of Apoptin is restricted to cancer cells, several recent studies have shown that Apoptin has the ability to migrate to the nucleus and induce PCD in some of the normal cell lines tested. There is evidence that high protein expression levels as well as the cellular growth rate may influence Apoptin's ability to specifically kill tumor cells. Thus far both in vitro and in vivo studies indicate that Apoptin is a powerful apoptosis inducing protein with a promising prospective utility in cancer therapy. However, here we show that several recent findings contradict some of the earlier results on the tumor specificity of Apoptin, thus creating some controversy in the field. The aim of this article is to review the available data, some published and some unpublished, which either agree or contradict the reported "black and white" tumor cell specificity of Apoptin. Understanding what factors appear to influence its function should help to develop Apoptin into a potent anti-cancer agent.
Tavassoli
M
M
Head and Neck Oncology Group, Department of Oral Medicine and Pathology, King's College London, 123 Coldharbour Lane, London SE5 9NU, UK. mahvash.tavassoli@kcl.ac.uk
Guelen
L
L
Luxon
B A
BA
Gäken
J
J
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D036022:Capsid Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000473:pathology*; D011485:Protein Binding
D051017:Apoptosis Regulatory Proteins; D036022:Capsid Proteins; C091717:VP3 protein, Chicken anemia virus