Latent membrane protein 1 of Epstein-Barr virus plays an important role in the serum starvation resistance of Epstein-Barr virus-immortalized B lymphocytes.
We have previously shown that SNU-1103, which is a latency type III Epstein-Barr virus (EBV)-transformed lymphoblastoid cell line (LCL) that was developed from a Korean cancer patient, resists serum starvation-induced G(1) arrest. In this study, we examined the role of latent membrane protein-1 (LMP-1) in serum starvation resistance, since LMP-1 is known to be essential for EBV-mediated immortalization of human B lymphocytes. The LMP-1 gene from SNU-1103 was introduced into the EBV-negative BJAB cell line, and shown to be associated with resistance to G(1) arrest during serum starvation. Western blot analyses of the LMP-1-transfected cells revealed several protein alterations as compared to vector-transfected control cells. The expression of key cell-cycle regulatory proteins was affected in the G(1) phase: the expression of cyclin D3, CDK2, p27, and E2F-4 was up-regulated, and the expression of cyclin D2, CDK6, p21, and p103 was down-regulated during serum starvation. These results imply that of the several EBV viral genes expressed in EBV-negative B lymphoma cells, LMP-1 mediates resistance to serum starvation-induced G(1) arrest. However, we cannot rule out the possibility that other EBV genes are also involved in the cell-cycle progression of the EBV-transformed LCL during serum starvation, since the altered protein expression profile of the LMP-1 transfectants was distinct from that of the SNU-1103 cells that expressed all of the EBV viral proteins.
Park
Chan-Hee
CH
Division of Biological Sciences and the Institute for Molecular Biology and Genetics, Chonbuk National University, Chonju 561-756, Korea.
Kim
Hak-Ryul
HR
Kim
Ju
J
Jang
Sun-Hee
SH
Lee
Kyung-Yeol
KY
Chung
Gook-Hyun
GH
Jang
Yong-Suk
YS
D001402:B-Lymphocytes / Q000187:drug effects* / Q000473:pathology* / Q000821:virology; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral / Q000187:drug effects*; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D050704:E2F4 Transcription Factor; D005786:Gene Expression Regulation / Q000187:drug effects; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D016160:Retinoblastoma Protein / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D016895:Culture Media, Serum-Free; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D050704:E2F4 Transcription Factor; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D014763:Viral Matrix Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases