Human tumor suppressor p53 and DNA viruses

Collot-Teixeira, Sophie; Bass, Juan I. Fuxman; Denis, François; Ranger-Rogez, Sylvie

doi:10.1002/rmv.431

Cited by 61 publications

(49 citation statements)

References 184 publications

(170 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 Generally, the regulation of p53 functions by viral oncoproteins involves mainly the alteration of its post-translational modifications ubiquitylation, acetylation or phosphorylation. 2 Kaposi's sarcoma-associated herpesvirus (KSHV) encodes several proteins that can compromise p53 activity, including the latency-associated nuclear antigen 2 (LANA2) (also called vIRF3).…”

Section: Introductionmentioning

confidence: 99%

KSHV latent protein LANA2 inhibits sumo2 modification of p53

et al. 2015

View full text Add to dashboard Cite

Tumor suppressor p53 plays a crucial antiviral role and targeting of p53 by viral proteins is a common mechanism involved in virus oncogenesis. The activity of p53 is tightly regulated at the post-translational levels through a myriad of modifications. Among them, modification of p53 by SUMO has been associated with the onset of cellular senescence. Kaposi´s sarcoma-associated herpesvirus (KSHV) expresses several proteins targeting p53, including the latent protein LANA2 that regulates polyubiquitylation and phosphorylation of p53. Here we show that LANA2 also inhibits the modification of p53 by SUMO2. Furthermore, we show that the reduction of p53-SUMO2 conjugation by LANA2, as well as the p53-LANA2 interaction, both require the SUMOylation of the viral protein and its interaction with SUMO or SUMOylated proteins in a non-covalent manner. Finally, we show that the control of p53-SUMO2 conjugation by LANA2 correlates with its ability to inhibit SUMO2-and type I interferon-induced senescence. These results highlight the importance of p53 SUMOylation in the control of virus infection and suggest that viral oncoproteins could contribute to viral infection and cell transformation by abrogating p53 SUMOylation.

show abstract

Section: Introductionmentioning

confidence: 99%

KSHV latent protein LANA2 inhibits sumo2 modification of p53

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Herpes simplex virus 1 (HSV-1) induces phosphorylation of p53 at Ser15 and 20 (Boutell & Everett, 2004;Shirata et al, 2005), and Epstein-Barr virus (EBV) induces phosphorylation at Ser6, 9, 15, 33, 46, 315 and 392 (Mauser et al, 2002;Kudoh et al, 2005). Nevertheless, knowledge regarding human herpesvirus-induced p53 phosphorylation is limited (Collot-Teixeira et al, 2004), and even less is known about the kinases responsible for the virusinduced phosphorylation events on p53.…”

Section: Introductionmentioning

confidence: 99%

Human herpesvirus 6B induces phosphorylation of p53 in its regulatory domain by a CK2- and p38-independent pathway

Øster

Bundgaard

Hupp

et al. 2008

Journal of General Virology

View full text Add to dashboard Cite

Here, we demonstrate that human herpesvirus 6B (HHV-6B) infection upregulates the tumour suppressor p53 and induces phosphorylation of p53 at Ser392. Interestingly, phosphorylation at the equivalent site has previously been shown to correlate with p53 tumour suppression in murine models. Although the signalling pathways leading to Ser392 phosphorylation are poorly understood, they seem to include casein kinase 2 (CK2), double-stranded RNA-activated protein kinase (PKR), p38 or cyclin-dependent kinase 9 (Cdk9). By using column chromatography and in vitro kinase assays, CK2 and p38, but not PKR or Cdk9, eluted in column fractions that phosphorylated p53 at Ser392. However, treatment of cells with neither the CK2 and Cdk9 inhibitor 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole (DRB) nor p38 kinase inhibitors reduced HHV-6B-induced Ser392 phosphorylation significantly. Knockdown of the CK2β subunit or p38α by small interfering RNA had no effect on HHV-6B-induced phosphorylation of p53 at Ser392. Thus, HHV-6B induces p53 Ser392 phosphorylation by an atypical pathway independent of CK2 and p38 kinases, whereas mitogen-activated protein (MAP) kinase signalling pathways are involved in viral replication.

show abstract

“…Inactivation of p53 protein can be induced by some viruses implicated in the development of cancer (6,31) as one of the viral mechanisms to inhibit apoptosis and prolong the survival of the virus. However, viruses with no tumorigenic potential and double-stranded RNA (dsRNA) have also been shown to downregulate p53 (14,25), suggesting the importance of p53 in host response to viruses.…”

mentioning

confidence: 99%