Apoptin, a tumor-selective killer.
Apoptin, a small protein from chicken anemia virus, has attracted great attention, because it specifically kills tumor cells while leaving normal cells unharmed. The subcellular localization of apoptin appears to be crucial for this tumor-selective activity. In normal cells, apoptin resides in the cytoplasm, whereas in cancerous cells it translocates into the nucleus. The nuclear translocation of apoptin is largely controlled by its phosphorylation. In tumor cells, apoptin causes the nuclear accumulation of survival kinases including Akt and is phosphorylated by CDK2. Thereby, apoptin redirects survival signals into cell death responses. Apoptin also binds as a multimeric complex to DNA and interacts with several nuclear targets, such as the anaphase-promoting complex, resulting in a G2/M phase arrest. The proapoptotic signal of apoptin is then transduced from the nucleus to cytoplasm by Nur77, which triggers a p53-independent mitochondrial death pathway. In this review, we summarize recent discoveries of apoptin's mechanism of action that might provide intriguing insights for the development of novel tumor-selective anticancer drugs.
Interfaculty Institute for Biochemistry, University of Tübingen, D-72076 Tübingen, Germany. mjelos@gmail.com
Marek
M
Los
Soumya
S
Panigrahi
Iran
I
Rashedi
Sanat
S
Mandal
Joerg
J
Stetefeld
Frank
F
Essmann
Klaus
K
Schulze-Osthoff
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017727:Chicken anemia virus / Q000737:chemistry / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D002645:Chickens; D018173:Circoviridae Infections / Q000473:pathology / Q000662:veterinary / Q000821:virology; D005814:Genes, Viral; D008954:Models, Biological; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011201:Poultry Diseases / Q000473:pathology / Q000821:virology; D001357:Sarcoma, Avian / Q000473:pathology
D036022:Capsid Proteins; C091717:VP3 protein, Chicken anemia virus