c-Jun and p53 Activity Is Modulated by SUMO-1 Modification

Müller, Stefan; Berger, Michael; Lehembre, François; Seeler, Jacob-S.; Haupt, Ygal; Dejean, Anne

doi:10.1074/jbc.275.18.13321

Cited by 370 publications

(312 citation statements)

References 36 publications

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“…Phosphorylation could also account for the coexistence of the nonsumoylated and sumoylated forms of RGSZ1 and GAIP. Indeed, proteins like heat stress factor 1 must be phosphorylated to undergo efficient sumoylation (Hietakangas et al, 2003), although the contrary has been observed for the transcription factor c-Jun, the sumoylation of which is downregulated after phosphorylation (Müller et al, 2000). As sumoylation can be regulated by phosphorylation, it is possible that phosphorylation of critical residues on RGSZ1 impairs SUMO conjugation.…”

Section: Discussionmentioning

confidence: 99%

Sumoylated RGS-Rz Proteins Act as Scaffolds for Mu-Opioid Receptors and G-Protein Complexes in Mouse Brain

Rodríguez-Muñoz

Bermúdez

Sánchez‐Blázquez

et al. 2006

Neuropsychopharmacol

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The RGSZ1 and RGSZ2 proteins, members of the RGS-Rz subfamily of GTPase-activating proteins (GAP), are involved in Mu-opioid receptor desensitization. The expression of these proteins, as well as of their main target the Gz protein, is virtually restricted to the nervous tissue. In synaptosomal membranes, these Rz proteins undergo post-translational modifications such as glycosylation and phosphorylation, and they may covalently attach to small ubiquitin-like modifier (SUMO) proteins. While RGSZ1 exists in conjugated and non-conjugated forms, RGSZ2 is mostly conjugated to SUMO-1, SUMO-2 and SUMO-3 proteins. These sumoylated forms of the GAPs readily associated with Mu-opioid receptors but they associated only poorly with Delta receptors. Furthermore, Gai2 and Gaz subunits co-precipitated with the sumoylated forms of RGSZ1/Z2 proteins, but to a lesser extent with the Ser phosphorylated SUMO-free form of RGSZ1. Upon Mu-opioid receptor activation, there is a strong increase in the association of Ga proteins with RGSZ2 proteins that persists for intervals longer than 24 h. This effect probably accounts for their role in Mu-opioid receptor desensitization. Only a moderate increase was observed with RGSZ1, the non-sumoylated form of which probably acts as an efficient GAP for these Ga subunits. Therefore, sumoylation regulates the biological activity of RGS-Rz proteins and it is likely that it serves to switch their behavior, from that of a GAP for activated Ga subunits to that of a scaffold protein for specific signaling proteins.

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Section: Discussionmentioning

confidence: 99%

Sumoylated RGS-Rz Proteins Act as Scaffolds for Mu-Opioid Receptors and G-Protein Complexes in Mouse Brain

Rodríguez-Muñoz

Bermúdez

Sánchez‐Blázquez

et al. 2006

Neuropsychopharmacol

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“…12,14,15 Furthermore, SUMOylation of p53 is induced in response to DNA damage, interferon treatment, or viral infection, and SUMOylation has an important role in the induction of senescence by p53, 12,13,16,17 suggesting that this modification may represent a physiological response to activate p53 after virus infection. Thus, it is possible to speculate that inhibition of p53 SUMOylation may be a mechanism used by viral proteins to control p53 activity.…”

Section: Resultsmentioning

confidence: 99%

KSHV latent protein LANA2 inhibits sumo2 modification of p53

et al. 2015

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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.

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“…The extreme C terminus of the protein controls its sequence-specific DNA binding and transcriptional activity, and these functions can be influenced by a multitude of covalent and non-covalent modifications within the C terminus. Modifications suggested to be involved in activation of p53 include sumoylation (Gostissa et al, 1999;Rodriguez et al, 1999;Muller et al, 2000), phosphorylation, dephosphorylation, acetylation, glycosylation (Shaw et al, 1996), ribosylation (Vaziri et al, 1997;Wang et al, 1998;Simbulan-Rosenthal et al, 1999) and redox regulation.…”

Section: Regulation Of P53 Activitymentioning

confidence: 99%

Activation and activities of the p53 tumour suppressor protein

Bálint¹,

Vousden²

2001

Br J Cancer

269

178

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The p53 tumour suppressor protein inhibits malignant progression by mediating cell cycle arrest, apoptosis or repair following cellular stress. One of the major regulators of p53 function is the MDM2 protein, and multiple forms of cellular stress activate p53 by inhibiting the MDM2-mediated degradation of p53. Mutations in p53, or disruption of the pathways that allow activation of p53, seem to be a general feature of all cancers. Here we review recent advances in our understanding of the pathways that regulate p53 and the pathways that are induced by p53, as well as their implications for cancer therapy. © 2001 Cancer Research Campaign http://www.bjcancer.com

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c-Jun and p53 Activity Is Modulated by SUMO-1 Modification

Cited by 370 publications

References 36 publications

Sumoylated RGS-Rz Proteins Act as Scaffolds for Mu-Opioid Receptors and G-Protein Complexes in Mouse Brain

Sumoylated RGS-Rz Proteins Act as Scaffolds for Mu-Opioid Receptors and G-Protein Complexes in Mouse Brain

KSHV latent protein LANA2 inhibits sumo2 modification of p53

Activation and activities of the p53 tumour suppressor protein

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