Epstein-Barr virus latent membrane protein 1 increases chemo-resistance of cancer cells via cytoplasmic sequestration of Pim-1.
Improved treatment of EBV positive lymphoma depends on the identification of molecular mechanism underlying chemo-resistance. LMP1 is an essential transmembrane protein for EBV-induced immortalization of hematopoietic cells. Herein, we show that an oncogenic Pim-1 is translocated to the cytoplasm by LMP1. Three lines of evidence indicate that cytoplasmic sequestration of Pim-1 may be required for LMP1-induced cancer cell survival. First, Pim-1 enhanced the survival of LMP1-overexpressing cells treated with doxorubicin. Second, nuclear export of Pim-1 was sufficient to increase the survival. Third, knockdown of Pim-1 effectively suppressed LMP-1-induced survival of cancer cells. Collectively, these data suggest that Pim-1 is a downstream target of LMP1, and that it contributes to the chemo-resistance of cancer cells.
Kim
Joo Hyun
JH
Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Kim
Won Seog
WS
Yun
Yungdae
Y
Park
Chaehwa
C
D021581:Active Transport, Cell Nucleus / Q000235:genetics / Q000276:immunology; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D003593:Cytoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D018274:Electroporation; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D051573:Proto-Oncogene Proteins c-pim-1 / Q000378:metabolism*; D014162:Transfection; D014763:Viral Matrix Proteins / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C496634:PIM1 protein, human; D051573:Proto-Oncogene Proteins c-pim-1