Processing of the Epstein-Barr virus-encoded latent membrane protein p63/LMP

Moorthy, Ramkumar; Thorley‐Lawson, David A.

doi:10.1128/jvi.64.2.829-837.1990

Cited by 39 publications

(17 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The carboxy-terminal domain may interact with cellular proteins that in turn facilitate the function of the transmembrane domain, or it may interact with other domains of LMP. This carboxy-terminal region is rich in aspartic acid and serine residues but does not contain the major sites of serine and threonine phosphorylation of LMP (40). It contains two potential SH3-binding motifs of the PXXP class, PHLP and PHGP, which could mediate binding events with cellular proteins.…”

Section: Discussionmentioning

confidence: 99%

“…The attachment of LMP to the cytoskeleton, localization to patches in the plasma membrane, and its short half-life (2,33,36) correlate with the oncogenic activity of LMP (37) and are properties that are reminiscent of activated growth factor receptors. The carboxy terminus of LMP is phosphorylated on serine and threonine residues and is proteolytically cleaved during the turnover of LMP (2,36,40), but these properties are dissociable from its oncogenic function (4,37,41).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Stimulation of NF-kappa B-mediated transcription by mutant derivatives of the latent membrane protein of Epstein-Barr virus

Mitchell

Sugden

1995

J Virol

261

109

View full text Add to dashboard Cite

The latent membrane protein (LMP) of Epstein-Barr virus contributes to the immortalizing activity of the virus in primary, human B lymphocytes, but its mechanism of function is unknown. LMP is expressed at the plasma membrane and may act by influencing the signalling pathways of infected cells. LMP increases transcription of reporter plasmids that are responsive to members of the NF-B/Rel family of transcription factors (M.-L. Hammarskjold and M. C. Simurda, J. Virol. 66:6496-6501, 1992, and A. Krikos, C. D. Laherty, and V. M. Dixit, J. Biol. Chem. 267:17971-17976, 1992). We measured the stimulation of the activity of a reporter plasmid by LMP in Jurkat and 293 cells in transfection experiments. Expression of LMP stimulated plasmids that contained B enhancer elements but not plasmids that lacked the elements. In 293 cells, expression of the NF-B inhibitor, IB-␣, reduced the stimulatory activity of LMP.We used deletional analysis to map the domains of LMP that are required for its activity in 293 cells. Wild-type LMP stimulated NF-B by a factor of 20 to 30, while mutant derivatives of LMP that lack oncogenic activity stimulated NF-B by a factor of 3. The multiple membrane-spanning segments together with the carboxy-terminal 55 amino acid residues of LMP were required for its maximal stimulatory function. Residues within its cytoplasmic amino terminus were not required for LMP's stimulation of NF-B.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Stimulation of NF-kappa B-mediated transcription by mutant derivatives of the latent membrane protein of Epstein-Barr virus

Mitchell

Sugden

1995

J Virol

261

109

View full text Add to dashboard Cite

show abstract

“…This mutant is not phosphorylated and can be cleaved, since p25 is detected in the cytoplasmic fraction of the cell expressing the NA43 mutant. However, the amount of p25 is severalfold lower than would be expected, considering the amount of the full-size NA43 protein, since as we have shown previously (18), 32P-labeled p25 is usually present at a 5to 10-fold excess over 32P-labeled LMP-1 (see, for example, the ratio in the unfractionated ER LCL control in Fig. 4).…”

Section: Resultsmentioning

confidence: 60%

“…The expression of all three mutants was confirmed initially by Western blotting (not shown) and subsequently by immunoprecipitation after 32P radiolabeling, since p25 cannot be detected by Western blotting (18). Figure 3 shows the result obtained with the A364-386 mutant.…”

Section: Resultsmentioning

confidence: 84%

“…LMP-1 has a very short half-life of 2 to 3 h (1, 15), and we have previously shown that the short half-life is due to specific cleavage of the C terminus of the protein (at leucine 242), which releases a 25,000-molecular-weight fragment (p25) into the cytoplasm and leaves a 35,000-molecular-weight fragment in the membrane (18). p25 is highly negatively charged and has phosphorylated serines and threonines in a ratio similar to that for LMP-1 (18).…”

mentioning

confidence: 96%

See 1 more Smart Citation

All three domains of the Epstein-Barr virus-encoded latent membrane protein LMP-1 are required for transformation of rat-1 fibroblasts

Moorthy

Thorley‐Lawson

1993

J Virol

Self Cite

157

View full text Add to dashboard Cite

LMP-1, the Epstein-Barr virus latent membrane protein 1, is the only protein encoded by the virus that has been shown to have the properties of a transforming oncogene in rodent fibroblasts such as Rat-1 cells. LMP-1 is phosphorylated and proteolytically cleaved in Rat-1 cells in a manner similar to that seen in human lymphocytes. In this study, we demonstrate that all three major domains of LMP-1 (N-terminal, transmembrane, and C-terminal domains) are required for the ability to transform Rat-i cells in culture, as assayed by loss of contact inhibition. This study is the first demonstration of a functional role for the C-terminal domain of LMP-1. Our analysis suggests that there are at least three distinct regions of the C terminus involved in signalling. Amino acids 306 to 334, which generate a toxic signal in the absence of amino acids 334 to 364, and the last 23 amino acids, 364 to 386, are essential for transformation. Biochemical analysis of the LMP-1 mutants with the three domains deleted indicate that the mutant N-terminal with the domain deleted is phosphorylated normally but is inefficiently cleaved compared with the wild-type LMP-1. The mutant with the transmembrane domain deleted is also phosphorylated but is not cleaved, showing that phosphorylation of LMP-1 does not require membrane association. The nontransforming mutant with the C-terminal domain deleted that lacks the last 23 amino acids is phosphorylated and cleaved. Therefore, these processing events alone are insufficient to generate a transforming signal.

show abstract

The Ubiquitin–Proteasome System in Epstein‐Barr Virus Infection and Oncogenesis

Masucci

2007

Protein Degradation Series

View full text Add to dashboard Cite

Processing of the Epstein-Barr virus-encoded latent membrane protein p63/LMP

Cited by 39 publications

References 30 publications

Stimulation of NF-kappa B-mediated transcription by mutant derivatives of the latent membrane protein of Epstein-Barr virus

Stimulation of NF-kappa B-mediated transcription by mutant derivatives of the latent membrane protein of Epstein-Barr virus

All three domains of the Epstein-Barr virus-encoded latent membrane protein LMP-1 are required for transformation of rat-1 fibroblasts

The Ubiquitin–Proteasome System in Epstein‐Barr Virus Infection and Oncogenesis

Contact Info

Product

Resources

About