Crucial roles for protein kinase C isoforms in tumor-specific killing by Apoptin

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)


The chicken anemia virus-derived protein apoptin induces apoptosis in a variety of human malignant and transformed cells but not in normal cells. However, the mechanisms through which apoptin achieves its selective killing effects are not well understood. We developed a lentiviral vector encoding a green fluorescent protein-apoptin fusion gene (LV-GFP-AP) that can efficiently deliver apoptin into hematopoietic cells. Apoptin selectively killed the human multiple myeloma cell lines MM1.R and MM1.S, and the leukemia cell lines K562, HL60, U937, KG1, and NB4. In contrast, normal CD34(+) cells were not killed and maintained their differentiation potential in multilineage colony formation assays. In addition, dexamethasone-resistant MM1.R cells were found to be more susceptible to apoptin-induced cell death than the parental matched MM1.S cells. Death susceptibility correlated with increased phosphorylation and activation of the apoptin protein in MM1.R cells. Expression array profiling identified differential kinase profiles between MM1.R and MM1.S cells. Among these kinases, protein kinase C beta (PKC beta) was found by immunoprecipitation and in vitro kinase studies to be a candidate kinase responsible for apoptin phosphorylation. Indeed, shRNA knockdown or drug-mediated inhibition of PKC beta significantly reduced apoptin phosphorylation. Furthermore, apoptin-mediated cell death proceeded through the upregulation of PKC beta, activation of caspase-9/3, cleavage of the PKC delta catalytic domain, and downregulation of the MERTK and AKT kinases. Collectively, these results elucidate a novel pathway for apoptin activation involving PKC beta and PKC delta. Further, they highlight the potential of apoptin and its cellular regulators to purge bone marrow used in autologous transplantation for multiple myeloma. Cancer Res; 70(18); 7242-52. (C)2010 AACR.
Original languageEnglish
Pages (from-to)7242 - 7252
Number of pages11
JournalCancer Research
Issue number18
Publication statusPublished - 15 Sept 2010


Dive into the research topics of 'Crucial roles for protein kinase C isoforms in tumor-specific killing by Apoptin'. Together they form a unique fingerprint.

Cite this