Modulation of p53-Mediated Transcriptional Repression and Apoptosis by the Adenovirus E1B 19K Protein

Sabbatini, Peter; Chiou, Shiun-Kwei; Rao, Lakshmi G.; White, Eileen

doi:10.1128/mcb.15.2.1060

Cited by 186 publications

(188 citation statements)

References 56 publications

Supporting

Mentioning

175

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, studies have also shown that antiapoptotic proteins such as Bcl-2 and adenovirus E1B 19-kD protein can inhibit p53-mediated apoptosis. Interestingly, these two proteins can also inhibit p53-mediated transrepression but not transactivation (Sabbatini et al, 1995a;Shen and Shenk, 1994). These results would be consistent with the transrepression function of p53 being associated with its apoptotic function.…”

Section: Uncoupling Of the Apoptotic Function Of P53 From Its Transacsupporting

confidence: 73%

mdm2: a bridge over the two tumour suppressors, p53 and Rb

et al. 1999

View full text Add to dashboard Cite

The inactivation of the p53 and Rb pathways would account for the majority of human tumours. There are many levels of cross talk between p53 and Rb that have been identi®ed. However, the identi®cation of the mdm2-Rb interaction established a closer link between the two most well studied tumour suppressors, p53 and Rb. Recent studies of the novel trimeric complex Rb-mdm2-p53 provided us with a functional insight of how the two tumour suppressors can act together in regulating p53 induced apoptosis. Beginning with the properties of the Rb-mdm2-p53 trimeric complex, we shall review the propounding evidence suggesting that the apoptotic function of p53 is linked to its transrepression function. The uncoupling of the apoptotic function and transactivation function of p53 will also be discussed.

show abstract

Section: Uncoupling Of the Apoptotic Function Of P53 From Its Transacsupporting

confidence: 73%

mdm2: a bridge over the two tumour suppressors, p53 and Rb

et al. 1999

View full text Add to dashboard Cite

show abstract

“…Among these genes, the viral genes E1B19kD and E1B55kD, cellular gene bcl2 and oncogenic cHa-ras that are complementing with E1A to fully transform cells of di erent origin. E1A+E1B19kD transformants expressing the wild type p53 reveal a p53-dependent block at G1/S boundary of the cell cycle (Sabbatini et al, 1995). In contrast, E1A+cHa-ras-transformed cells are unable to be arrested at G1/S by over-expression of wild type p53 (Lin et al, 1995).…”

Section: Introductionmentioning

confidence: 96%

“…High e ciency of foci formation in the presence of Ad5-E1A can be achieved when E1A cooperates with genes that suppress the programmed cell death allowing the E1A expression at high levels (Lin et al, 1995;Sabbatini et al, 1995). Among these genes, the viral genes E1B19kD and E1B55kD, cellular gene bcl2 and oncogenic cHa-ras that are complementing with E1A to fully transform cells of di erent origin.…”

Section: Introductionmentioning

confidence: 99%

Deregulation of p53/p21Cip1/Waf1 pathway contributes to polyploidy and apoptosis of E1A+cHa-ras transformed cells after γ-irradiation

et al. 1999

View full text Add to dashboard Cite

The p53/p21 Cip1/Waf1 -dependent checkpoint control of G1/S and G2/M phases of the cell cycle in response to DNA damage is an important mechanism of genome stability maintenance in normal cells. In many tumor cells, due to frequent point mutations and deletions of p53, the stringent control of the cell cycle and apoptosis is compromised. We have examined the cell cycle control and cell death of the rat embryo ®broblast cells (REF) transformed by E1A+cHa-ras oncogenes and expressing wild type p53. Gamma-irradiation at a dosage of 6 Gy has been used to analyse the p53-dependent transactivation of the target p21 cip1/waf1 gene and the levels of activity of cyclin-dependent kinases. Our results show that the cell cycle inhibitors p21 Cip1/Waf1 and p27 KIP accumulate in response to irradiation both in REF and E1A+cHa-ras cells. In contrast to normal REF cells, the accumulation of p21 Cip1/Waf1 and p27 KIP inhibitors, however, does not lead to inhibition of Cdk2 and cyclins E, A-associated kinase activities and to a G1/S block in E1A+cHa-ras cells. It is unlikely that the lack of inhibitory function of p21 Cip1/Waf1 can be explained by its inability to bind Cdk2 and Cdk4 kinases or PCNA. Moreover, the p21 Cip1/Waf1 -associated kinase activity is increased upon g-irradiation of E1A+cHa-ras cells. We suggest that inactivation of p21 Cip1/Waf1 may be accounted for by its interaction with E1A oncoproducts as the inhibitor is detected in immunoprecipitates using E1A-speci®c antibodies. During a temporary G2/M delay induced by g-irradiation, E1A+cHa-ras transformants continue DNA replication, which leads to accumulation of polyploid cells with lobulated nuclei and micronuclei. Thus, DNA damage of E1A+cHa-ras transformed cells, with a combination of functionally active wild type p53 and inactive p21 Cip1/Waf1 , contributes to formation of polyploid cells which then die due to apoptosis.

show abstract

“…However, at 328C the permissive temperature, p53 is wild-type and cells undergo apoptosis. Expression of the E1B 19K protein in the E1A plus p53(Val135) transformed BRK cell line can overcome apoptosis induced by wild-type p53 at 328C (Debbas and White, 1993) although, the ability of p53 to induce growth arrest is not a fected by the expression of E1B 19K (Sabbatini et al, 1995a).…”

Section: Introductionmentioning

confidence: 99%

The E1B 19K protein associates with lamins in vivo and its proper localization is required for inhibition of apoptosis

1997

View full text Add to dashboard Cite

Expression of the E1B 19K protein is required to inhibit apoptosis induced by E1A during adenovirus infection and transformation. E1B 19K is homologous to Bcl-2 in function and the two proteins also share limited amino acid sequence homology. Consequently, the E1B 19K and Bcl-2 proteins bind to and inhibit the cellular deathinducing proteins Bax, Bak and Nbk/Bik. Both E1B 19K and Bcl-2 localize to membranes of the nucleus and the endoplasmic reticulum. In addition to membrane association, and unlike Bcl-2, the E1B 19K protein is found associated with intermediate ®lament proteins in the cytoplasm and the nuclear lamina and copuri®es with the lamins both during infection and transformation. While a membrane targeting domain at the C-terminus of Bcl-2 ensures its proper localization, the mechanism by which the E1B 19K protein localizes is unknown. Not surprisingly, lamin A fragments were cloned from a yeast two-hybrid screen for E1B 19K-interacting proteins. The interaction was demonstrated in yeast and mammalian cells in vivo and in vitro and was unique and speci®c to E1B 19K, with no interaction evident between Bcl-2 and lamin A. Mutants of lamin A/C which localized inappropriately in the cytoplasm or nucleus but retained E1B 19K binding, interfered with the nuclear envelope and cytoplasmic membrane targeting of the E1B 19K protein. Improper localization impaired the ability of the E1B 19K protein to inhibit apoptosis. Thus, proper localization of the E1B 19K protein is required for its function and the interaction of the E1B 19K protein with lamin A/C may represent a means for nuclear envelope localization.

show abstract

Modulation of p53-Mediated Transcriptional Repression and Apoptosis by the Adenovirus E1B 19K Protein

Cited by 186 publications

References 56 publications

mdm2: a bridge over the two tumour suppressors, p53 and Rb

mdm2: a bridge over the two tumour suppressors, p53 and Rb

Deregulation of p53/p21Cip1/Waf1 pathway contributes to polyploidy and apoptosis of E1A+cHa-ras transformed cells after γ-irradiation

The E1B 19K protein associates with lamins in vivo and its proper localization is required for inhibition of apoptosis

Contact Info

Product

Resources

About