Regulation of p53 levels by the E1B 55-kilodalton protein and E4orf6 in adenovirus-infected cells

Emmanuelle Querido, Richard C. Marcellus, Albert Lai, Rachel Charbonneau, Jose G. Teodoro, Gary W Ketner, Philip E. Branton

Research output: Contribution to journalArticle

Abstract

The adenovirus type 5 243R E1A protein induces p53-dependent apoptosis in the absence of the 19- and 55-kDa E1B polypeptides. This effect appears to result from an accumulation of p53 protein and is unrelated to expression of E1B products. We now report that in the presence of the E1B 55-kDa polypeptide, the 289R E1A protein does not induce such p53 accumulation and, in fact, is able to block that induced by E1A 243R. This inhibition also requires the 289R-dependent transactivation of E4orf6 expression. E4orf6 is known to form complexes with the E1B 55-kDa protein and to function both in the transport and stabilization of viral mRNA and in shutoff of bust cell protein synthesis. We demonstrated that the block in p53 accumulation is not due to the generalized shutoff of host cell metabolism. Rather, it appears to result from a mechanism targeted specifically to p53, most likely involving a decrease in the stability of p53 protein. The E1B 55-kDa protein is known to interact with both E4orf6 and p53, and as demonstrated recently by others, we showed that E4orf6 also binds directly to p53. Thus, multiple interactions between all three proteins may regulate p53 stability, resulting in the maintenance of low levels of p53 following virus infection.

Original languageEnglish (US)
Pages (from-to)3788-3798
Number of pages11
JournalJournal of Virology
Volume71
Issue number5
StatePublished - May 1997

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Adenoviridae
Proteins
proteins
cells
polypeptides
Peptides
Protein Stability
Virus Diseases
Transcriptional Activation
transcriptional activation
adenovirus E4orf6 protein
Maintenance
Apoptosis
apoptosis
protein synthesis
Messenger RNA
viruses
metabolism
infection

ASJC Scopus subject areas

  • Immunology

Cite this

Querido, E., Marcellus, R. C., Lai, A., Charbonneau, R., Teodoro, J. G., Ketner, G. W., & Branton, P. E. (1997). Regulation of p53 levels by the E1B 55-kilodalton protein and E4orf6 in adenovirus-infected cells. Journal of Virology, 71(5), 3788-3798.

Regulation of p53 levels by the E1B 55-kilodalton protein and E4orf6 in adenovirus-infected cells. / Querido, Emmanuelle; Marcellus, Richard C.; Lai, Albert; Charbonneau, Rachel; Teodoro, Jose G.; Ketner, Gary W; Branton, Philip E.

In: Journal of Virology, Vol. 71, No. 5, 05.1997, p. 3788-3798.

Research output: Contribution to journalArticle

Querido, E, Marcellus, RC, Lai, A, Charbonneau, R, Teodoro, JG, Ketner, GW & Branton, PE 1997, 'Regulation of p53 levels by the E1B 55-kilodalton protein and E4orf6 in adenovirus-infected cells', Journal of Virology, vol. 71, no. 5, pp. 3788-3798.
Querido E, Marcellus RC, Lai A, Charbonneau R, Teodoro JG, Ketner GW et al. Regulation of p53 levels by the E1B 55-kilodalton protein and E4orf6 in adenovirus-infected cells. Journal of Virology. 1997 May;71(5):3788-3798.
Querido, Emmanuelle ; Marcellus, Richard C. ; Lai, Albert ; Charbonneau, Rachel ; Teodoro, Jose G. ; Ketner, Gary W ; Branton, Philip E. / Regulation of p53 levels by the E1B 55-kilodalton protein and E4orf6 in adenovirus-infected cells. In: Journal of Virology. 1997 ; Vol. 71, No. 5. pp. 3788-3798.
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