Domains required for in vitro association between the cellular p53 and the adenovirus 2 E1B 55k proteins

Kao, C. Y.; Yew, P.Renee; Berk, Arnold

doi:10.1016/0042-6822(90)90148-k

Cited by 183 publications

(169 citation statements)

References 51 publications

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“…First, E1B55K binds to the amino terminus of p53, thus inhibiting p53 transactivation. [6][7][8][9] Second, E1B55K, together with the Ad E4orf6 protein, degrades p53 protein in Ad-infected cells. [10][11][12] The E1B19K protein is a functional homologue of the antiapoptotic cellular protein, Bcl-2.…”

Section: T O Induce the Cells Into S-phase For Effective Viralmentioning

confidence: 99%

E1A-induced apoptosis does not prevent replication of adenoviruses with deletion of E1b in majority of infected cancer cells

et al. 2004

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Apoptotic pathways are initiated as a cellular defense mechanism to eliminate adenovirus-infected cells. We have investigated how E1A-induced apoptosis interferes with viral replication in cancer cells. We found that E1B19K alone can efficiently suppress E1A-induced apoptosis in cancer cells. Viruses deleted for both E1B19K and E1B55K resulted in cellular DNA degradation. However, less than 20% of human lung cancer cells infected with a virus deleted for both E1B19K and E1B55 K had evidence of chromatin condensation and multiple-micronuclei formation (apoptotic hallmarks); these cells could not produce infectious viral particles. The majority of cancer cells infected with viruses deleted for the entire E1b gene did not undergo extended apoptosis and produced abundant viral progeny. Thus, only a fraction of cancer cells underwent apoptosis and did not allow E1b-deleted viruses to replicate, while the majority of cancer cells were resistant to E1A-induced apoptosis and could support virus-selective replication. The results of this study imply that, in addition to inhibiting E1A-induced apoptosis, E1B proteins may contribute other important roles in the viral life cycle. Our results also suggest that combining virus-induced apoptosis and selective viral replication into one vector will be a novel approach to destroy cancer cells.

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Section: T O Induce the Cells Into S-phase For Effective Viralmentioning

confidence: 99%

E1A-induced apoptosis does not prevent replication of adenoviruses with deletion of E1b in majority of infected cancer cells

et al. 2004

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“…p53 (Kao et al, 1990;Yew and Berk, 1992;Yew et al, 1994). The E1B19K protein is a functional homologue of the proto-oncogene Bcl-2 and prevents apoptosis (Rao et al, 1992;Debbas and White, 1993).…”

Section: Cell Cycle Control By Dna-virusesmentioning

confidence: 99%

“…The E1B19K protein is a functional homologue of the proto-oncogene Bcl-2 and prevents apoptosis (Rao et al, 1992;Debbas and White, 1993). The E1B55K gene product is capable of binding p53 and inactivating it (Kao et al, 1990). Together with another early viral protein, the E4orf6 protein, E1B55K exports p53 to the cytoplasm and targets it for degradation (Moore et al, 1996;Querido et al, 1997).…”

Section: Cell Cycle Control By Dna-virusesmentioning

confidence: 99%

ONYX-015: mechanisms of action and clinical potential of a replication-selective adenovirus

2002

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Accumulated knowledge in the molecular processes of tumour development combined with the availability of genetically modified viruses resemble the basis for new promising cancer therapeutics. The main advantages of employing replicationcompetent viruses are achievement of tumour selective killing and amplification of their oncolytic potential within the tumour mass. In this review, we describe the development of ONYX-015, one of the first and most advanced replication-competent viruses for cancer therapy. We discuss the molecular biology of this therapeutic approach and the interesting results obtained with this virus in clinical trials.

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“…The pro-tumorigenic functions of the 55-kDa phosphoproteins encoded by the early region 1B (E1B-55K) of human adenoviruses are primarily linked to the modulation of the tumour suppressor p53 and consequently inhibition of programmed cell death and growth arrest. Subsequent steps of direct interaction (Sarnow et al, 1982a;Kao et al, 1990), transcriptional repression (Yew et al, 1994;Berk, 1998, 1999) and nuclear-cytoplasmic relocalization (Endter et al, 2001(Endter et al, , 2005 induce the complete silencing of p53-dependent tumour suppressive functions. However, previously described results suggest additional p53-independent mechanisms of E1B-55K induced cellular transformation involving cellular factors as Mre11 (Ha¨rtl et al, 2008) or the transcription factor Daxx (Sieber and Dobner, 2007).…”

Section: Introductionmentioning

confidence: 99%

SUMO modification of E1B-55K oncoprotein regulates isoform-specific binding to the tumour suppressor protein PML

Wimmer

Schreiner

Everett³

et al. 2010

Oncogene

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The E1B-55K product from human adenovirus is a substrate of the small ubiquitin-related modifier (SUMO)-conjugation system. SUMOylation of E1B-55K is required to transform primary mammalian cells in cooperation with adenovirus E1A and to repress p53 tumour suppressor functions. The biochemical consequences of SUMO1 conjugation of 55K have so far remained elusive. Here, we report that E1B-55K physically interacts with different isoforms of the tumour suppressor protein promyelocytic leukaemia (PML). We show that E1B-55K binds to PML isoforms IV and V in a SUMO1-dependent and -independent manner. Interaction with PML-IV promotes the localization of 55K to PMLcontaining subnuclear structures (PML-NBs). In virusinfected cells, this process is negatively regulated by other viral proteins, indicating that binding to PML is controlled through reversible SUMOylation in a timely coordinated manner. These results together with earlier work are consistent with the idea that SUMOylation regulates targeting of E1B-55K to PML-NBs, known to control transcriptional regulation, tumour suppression, DNA repair and apoptosis. Furthermore, they suggest that SUMO1-dependent modulation of p53-dependent growth suppression through E1B-55K PML-IV interaction has a key role in adenovirus-mediated cell transformation.

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Domains required for in vitro association between the cellular p53 and the adenovirus 2 E1B 55k proteins

Cited by 183 publications

References 51 publications

E1A-induced apoptosis does not prevent replication of adenoviruses with deletion of E1b in majority of infected cancer cells

E1A-induced apoptosis does not prevent replication of adenoviruses with deletion of E1b in majority of infected cancer cells

ONYX-015: mechanisms of action and clinical potential of a replication-selective adenovirus

SUMO modification of E1B-55K oncoprotein regulates isoform-specific binding to the tumour suppressor protein PML

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