Tags

Type your tag names separated by a space and hit enter

Response to cAMP levels of the Epstein-Barr virus EBNA2-inducible LMP1 oncogene and EBNA2 inhibition of a PP1-like activity.
EMBO J. 1994 Dec 15; 13(24):6041-51.EJ

Abstract

The expression of the Epstein-Barr virus LMP1 oncogene is regulated by viral and non-viral factors in a tissue dependent fashion. The virus encoded transcription factor EBNA2 induces its expression in human B-cells. However, this induction also requires the contribution of cellular and/or other viral factors. In nasopharyngeal carcinoma cells and in cells from Hodgkin's lymphoma, LMP1 gene transcription is independent of viral products. Here we show that the effect of a factor binding to a cAMP responsive-like element (CRE) in the LMP1 gene transcription regulatory sequence (LRS) is essential for efficient promoter activity in the DG75 B-cell line and that elevation of cAMP levels in the cells induces LRS-derived CAT activity in a CRE dependent fashion. Incubation of two EBV-immortalized B-cell lines expressing endogenous EBNA2A with 8-Br cAMP increased the levels of the latency associated 66 kDa LMP1 within 2 h. Interestingly, LMP1 expression in DG75 cells conferred resistance to the inhibitory effect of 8-Br cAMP on cell proliferation. The protein phosphatase 1 and 2A (PP1 and PP2A, respectively) inhibitor okadaic acid also stimulated LRS-CAT activity in DG75 cells. EBNA2A from an EBV-immortalized B-cell line co-immunopurified with a PP1-like protein. An EBNA2A fragment spanning residues 324-436 fused to the GST protein specifically rescued a PP1/PP2A-like component from DG75 cell extracts. This GST-EBNA2A fusion product inhibited a PP1-like activity in nuclear extracts from these cells.

Authors+Show Affiliations

Department of Medical Biochemistry, Göteborg University, Gothenburg, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7813442

Citation

Fåhraeus, R, et al. "Response to cAMP Levels of the Epstein-Barr Virus EBNA2-inducible LMP1 Oncogene and EBNA2 Inhibition of a PP1-like Activity." The EMBO Journal, vol. 13, no. 24, 1994, pp. 6041-51.
Fåhraeus R, Palmqvist L, Nerdstedt A, et al. Response to cAMP levels of the Epstein-Barr virus EBNA2-inducible LMP1 oncogene and EBNA2 inhibition of a PP1-like activity. EMBO J. 1994;13(24):6041-51.
Fåhraeus, R., Palmqvist, L., Nerdstedt, A., Farzad, S., Rymo, L., & Laín, S. (1994). Response to cAMP levels of the Epstein-Barr virus EBNA2-inducible LMP1 oncogene and EBNA2 inhibition of a PP1-like activity. The EMBO Journal, 13(24), 6041-51.
Fåhraeus R, et al. Response to cAMP Levels of the Epstein-Barr Virus EBNA2-inducible LMP1 Oncogene and EBNA2 Inhibition of a PP1-like Activity. EMBO J. 1994 Dec 15;13(24):6041-51. PubMed PMID: 7813442.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Response to cAMP levels of the Epstein-Barr virus EBNA2-inducible LMP1 oncogene and EBNA2 inhibition of a PP1-like activity. AU - Fåhraeus,R, AU - Palmqvist,L, AU - Nerdstedt,A, AU - Farzad,S, AU - Rymo,L, AU - Laín,S, PY - 1994/12/15/pubmed PY - 1994/12/15/medline PY - 1994/12/15/entrez SP - 6041 EP - 51 JF - The EMBO journal JO - EMBO J VL - 13 IS - 24 N2 - The expression of the Epstein-Barr virus LMP1 oncogene is regulated by viral and non-viral factors in a tissue dependent fashion. The virus encoded transcription factor EBNA2 induces its expression in human B-cells. However, this induction also requires the contribution of cellular and/or other viral factors. In nasopharyngeal carcinoma cells and in cells from Hodgkin's lymphoma, LMP1 gene transcription is independent of viral products. Here we show that the effect of a factor binding to a cAMP responsive-like element (CRE) in the LMP1 gene transcription regulatory sequence (LRS) is essential for efficient promoter activity in the DG75 B-cell line and that elevation of cAMP levels in the cells induces LRS-derived CAT activity in a CRE dependent fashion. Incubation of two EBV-immortalized B-cell lines expressing endogenous EBNA2A with 8-Br cAMP increased the levels of the latency associated 66 kDa LMP1 within 2 h. Interestingly, LMP1 expression in DG75 cells conferred resistance to the inhibitory effect of 8-Br cAMP on cell proliferation. The protein phosphatase 1 and 2A (PP1 and PP2A, respectively) inhibitor okadaic acid also stimulated LRS-CAT activity in DG75 cells. EBNA2A from an EBV-immortalized B-cell line co-immunopurified with a PP1-like protein. An EBNA2A fragment spanning residues 324-436 fused to the GST protein specifically rescued a PP1/PP2A-like component from DG75 cell extracts. This GST-EBNA2A fusion product inhibited a PP1-like activity in nuclear extracts from these cells. SN - 0261-4189 UR - https://www.unboundmedicine.com/medline/citation/7813442/Response_to_cAMP_levels_of_the_Epstein_Barr_virus_EBNA2_inducible_LMP1_oncogene_and_EBNA2_inhibition_of_a_PP1_like_activity_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0261-4189&date=1994&volume=13&issue=24&spage=6041 DB - PRIME DP - Unbound Medicine ER -