This 121-residue nucleocytoplasmic shuttling protein (MW = 13.6 kDa; GenBank: AAO45416.1), from Chicken Anemia Virus (CAV) and Human Gyrovirus Type 1, associates with APC (anaphase-promoting complex), inducing G2/M cell-cycle arrest and apoptosis in the absence of p53. When grown in vitro, CAV only replicates in transformed chicken cell lines, suggesting that at least a part of the CAV life-cycle requires transformation-like cellular events. Apoptin triggers programmed cell death by activating the mitochondrial pathway (or intrinsic apoptosis), acting independently of the death receptor pathway (or extrinsic apoptosis). Synthesis of apoptin alone induces apoptosis in various human transformed and/or tumorigenic cell lines, but not in normal human diploid cells. Apoptin also interacts with the SH3 domain of the BCR-ABL1 fusion protein, inhibiting BCR-ABL1 kinase and its downstream targets. A chimeric protein (Dose: 1 μM), consisting of apoptin fsed the Tat cell- penetrating sequence, as well as the apoptin-derived decapeptide (Sequence: PKPPSKKRSC; Dose: 1-2 μM), but not the sequence- scrambled peptide PRPPSRSPKC, is effective in treating chronic myelogenous leukemia (CML) by inhibiting the BCR-ABL1 down-stream target, c-Myc, with an efficacy comparable to full-length apoptin and imatinib (See Imatinib). Synthetic apoptin inhibits cell proliferation in murine 32Dp210 cells and human K562 cells, and is also effective ex vivo in both imatinib-resistant and imatinib-sensitive CML patient samples.
