Porcine circovirus type 2 ORF3 protein competes with p53 in binding to Pirh2 and mediates the deregulation of p53 homeostasis

Karuppannan, Anbu K.; Liu, Sen; Jia, Qiang; Selvaraj, Manikandan; Kwang, Jimmy

doi:10.1016/j.virol.2009.11.028

Cited by 33 publications

(41 citation statements)

References 44 publications

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“…The ORF3 protein inhibits stabilization of porcine ubiquitin E3 ligase Pirh2 (pPirh2) by specifically interacting with the protein [35,83,85,86]. Further studies indicated that the apoptotic responses are mainly induced by the C-terminal half of ORF3, which might correlate with the nuclear localization of ORF3 [87].…”

Section: Pcv2-induced Cell Apoptosismentioning

confidence: 99%

Interactions of porcine circovirus 2 with its hosts

2016

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Porcine circovirus 2 (PCV2) can cause porcine circovirus diseases and porcine circovirus-associated diseases (PCVD/PCVAD), which are widely presented in swine-producing countries. Since the discovery of this virus, considerable efforts have been devoted to understanding this pathogen and its interactions with its host. Here, we review the current state of knowledge on interactions between host cell factors and PCV2 with respect to viral proliferation, virus-induced cell apoptosis and autophagy, and host antiviral defenses during PCV2 infection. We also review mouse model systems for PCV2 infection.

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Section: Pcv2-induced Cell Apoptosismentioning

confidence: 99%

Interactions of porcine circovirus 2 with its hosts

2016

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“…( 96,97 ) Measles virus phosphoprotein and porcine circovirus type 2 open reading frame 3 are two pathogenic proteins that affect the stability of Pirh2. ( 98–100 )…”

Section: Regulation Of Pirh2 Activitymentioning

confidence: 99%

A novel oncoprotein Pirh2: rising from the shadow of MDM2

et al. 2011

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Pirh2 (p53-induced RING-H2) is an E3 ubiquitin ligase that can target p53 for degradation and thereby repress a diverse group of biological activities regulated by p53. Notably, Pirh2, rather than MDM2, is the primary degrader of active p53 under conditions of DNA damage. Moreover, Pirh2 is highly expressed in multiple cancer cell lines regardless of p53 status. Recent research has shown that Pirh2 is involved in many signalling pathways related to the genesis and evolution of cancer. This review aims to summarize a comprehensive picture of the role of Pirh2 in cellular processes and its significance to tumorigenesis. Furthermore, this review focuses on its potential role as a cancer therapeutic target. (Cancer Sci 2011; 102: 909-917) T he tumor suppressor p53, known as ''the guardian of the genome'', plays a key role in eliciting cellular responses to many signals of cell stress. Upon activation, p53 can affect cellular functions including transcription, DNA synthesis and repair, cell cycle arrest, senescence and apoptosis. Recent studies have demonstrated that p53 also influences metabolism and angiogenesis, regulates cell motility and immune responses and mediates cell-cell communication.(1) By promoting cell cycle arrest, apoptosis, senescence and DNA repair, p53 helps prevent cancer development. (2,3) The importance of p53 in tumor suppression is highlighted by the abundant, inactivating, somatic p53 mutations that are found in more than 50% of human cancer cells.(4) p53 is subjected to a variety of post-translational modifications, including phosphorylation, acetylation, ubiquitylation and methylation. (5,6) Ubiquitylation is an important mechanism for controlling p53 activity. (7) Pirh2, first identified as an androgen receptor N-terminalinteracting protein (ARNIP) (8) and also known as ring finger and CHY zinc finger domain-containing 1 (Rchy1), is a member of the RING finger family of E3 ubiquitin ligases, which can facilitate protein degradation via the ubiquitin-proteasome pathway.(9) The RING domain of Pirh2 contains a RING-H2 (Cys 3 His 2 Cys 3 ) motif, which is critical for maintaining the functions of several important E3 ubiquitin ligases including c-Cbl, anaphase-promoting complex (APC) and SCF complexes. (10)(11)(12) The N-terminal lobe of the Pirh2 N-terminal domain is a member of the CHY zinc finger family (Fig. 1).(13) Currently, the best understood function of Pirh2 is its role in the Pirh2-p53 feedback loop that is independent of MDM2. Pirh2 is transcriptionally activated by p53, and Pirh2, in turn, inhibits p53 activity in several ways. Notably, Pirh2 has been shown to degrade active p53 under conditions of DNA damage when MDM2 dissociates from and fails to degrade p53. (14) In addition, the disruption of Pirh2 homeostasis is closely related to the formation of various human tumors (Table 1). (15)(16)(17)(18)(19)(20)(21)(22) Rchy1 is one of the key genes related to the locoregional recurrence control of breast cancer, (23,24) and Pirh2 was elevated in approximately 93% of all murine l...

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“…PCV2 have non-enveloped icosahedral virion with a size of 17 nm and containing single-stranded circular deoxyribonucleic acid (DNA) genome of 1,767-1,768 nucleotides (nt) [1,2]. PCV2 have three major open reading frames (ORF), ORF1-3 [1,2,3]. The ORF1 encodes two major replication associated proteins: the complete Rep, and the spliced form Rep, which has a frame shift Rep′ [1].…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, some variable amino acid residues located in the putative epitopes of ORF2 are exposed outside the virion, and these residues are suggested to be constantly under positive or negative selection forces due to constant exposure to high immunologic pressure [2,4]. The ORF3 encodes a protein that has been implicated with cellular apoptosis in the porcine kidney PK-15 cell line, as well as in peripheral blood mononuclear cells [3].…”

Section: Introductionmentioning

confidence: 99%

Retrospective Study of Porcine Circovirus Type 2a and 2b Between 1999 and 2016 in Taiwan

Lee¹

2017

AVS

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Porcine circovirus type 2 (PCV2) is one of the major swine viral diseases and caused significant economic loss to pig producers worldwide, including Taiwan. PCV2 has been considered as the causative agent of postweaning multisystemic wasting syndrome (PMWS) as well as other clinical diseases. All these associated syndromes have been categorized as PCV2 associated diseases (PCVAD). The purpose of this study was to investigate the positive rate and genetic shift of two distinct genotypes of PCV2, which include PCV2a and PCV2b, in Taiwanese pig farms. A total of 1094 specimens originating from pigs between years 1999 and 2016 were analysed. The PCV2a and PCV2b sequences were amplified and distinguished using 1oop-mediated isothermal amplification (LAMP). Results showed that 24.8% (272/1094) pigs were PCV2a positive, 67.3% (737/1094) were PCV2b positive. These results also indicated that PCV2a was the predominant virus between 1999 and 2001, and that PCV2b became the most prevalent virus since 2003.

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Porcine circovirus type 2 ORF3 protein competes with p53 in binding to Pirh2 and mediates the deregulation of p53 homeostasis

Cited by 33 publications

References 44 publications

Interactions of porcine circovirus 2 with its hosts

Interactions of porcine circovirus 2 with its hosts

A novel oncoprotein Pirh2: rising from the shadow of MDM2

Retrospective Study of Porcine Circovirus Type 2a and 2b Between 1999 and 2016 in Taiwan

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