p32/gC1qR is indispensable for fetal development and mitochondrial translation: importance of its RNA-binding ability

Yagi, Minoru; Uchiumi, Takeshi; Takazaki, Shinya; Okuno, Bungo; Nomura, Masatoshi; Yoshida, Shin Ichi; Kanki, Tomotake; Kang, Dongchon

doi:10.1093/nar/gks774

Cited by 139 publications

(221 citation statements)

References 55 publications

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“…Phosphorylation of p32/gC1qR by the viral kinase pUL97 was demonstrated previously (33). In the present work, p32/gC1qR localization changed from a tubular cytoplasmic localization (mitochondria-associated in mock-infected cells) (36) to a punctate, granular-shaped cytoplasmic localization with some faint staining in the nucleus of infected cells (Fig. 4, panels l-p).…”

Section: Identification Of Postulated Components Of the Hcmv-specificsupporting

confidence: 82%

Proteomic Analysis of the Multimeric Nuclear Egress Complex of Human Cytomegalovirus

Milbradt

Kraut

Hutterer

et al. 2014

Molecular & Cellular Proteomics

110

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Herpesviral capsids are assembled in the host cell nucleus before being translocated into the cytoplasm for further maturation. The crossing of the nuclear envelope represents a major event that requires the formation of the nuclear egress complex (NEC). Previous studies demonstrated that human cytomegalovirus (HCMV) proteins pUL50 and pUL53, as well as their homologs in all members of Herpesviridae, interact with each other at the nuclear envelope and form the heterodimeric core of the NEC. In order to characterize further the viral and cellular protein content of the multimeric NEC, the native complex was isolated from HCMV-infected human primary fibroblasts at various time points and analyzed using quantitative proteomics. Previously postulated components of the HCMVspecific NEC, as well as novel potential NEC-associated proteins such as emerin, were identified. In this regard, interaction and colocalization between emerin and pUL50 were confirmed by coimmunoprecipitation and confocal microscopy analyses, respectively. A functional validation of viral and cellular NEC constituents was achieved through siRNA-mediated knockdown experiments. The important role of emerin in NEC functionality was demonstrated by a reduction of viral replication when emerin expression was down-regulated. Moreover, under such conditions, reduced production of viral proteins and deregulation of viral late cytoplasmic maturation were observed. Combined, these data prove the functional importance of emerin as an NEC component, associated with pUL50, pUL53, pUL97, p32/ gC1qR, and further regulatory proteins. Summarized, our findings provide the first proteomics-based characterization and functional validation of the HCMV-specific multimeric NEC. Molecular & Cellular

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Section: Identification Of Postulated Components Of the Hcmv-specificsupporting

confidence: 82%

Proteomic Analysis of the Multimeric Nuclear Egress Complex of Human Cytomegalovirus

Milbradt

Kraut

Hutterer

et al. 2014

Molecular & Cellular Proteomics

110

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“…The interaction of UL47 with p32 was confirmed in HSV-1-infected cells: p32 coprecipitated with MEF-tagged UL47 in lysates of cells infected with recombinant virus YK536 (MEF-UL47). p32 is a ubiquitous protein in most cell types and a multifunctional protein regulating various cellular functions, including apoptosis, RNA splicing, mitochondrial translation and metabolism, and autophagy (27,(59)(60)(61)(62). We also found that p32 accumulated at the nuclear rim in HSV-1-infected cells and that UL47 was required for the p32 accumulation.…”

Section: Discussionmentioning

confidence: 63%

Role of Host Cell p32 in Herpes Simplex Virus 1 De-Envelopment during Viral Nuclear Egress

Liu

Kato

Oyama

et al. 2015

J Virol

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To clarify the function(s) of the herpes simplex virus 1 (HSV-1) major virion structural protein UL47 (also designated VP13/14), we screened cells overexpressing UL47 for UL47-binding cellular proteins. Tandem affinity purification of transiently expressed UL47 coupled with mass spectrometry-based proteomics technology and subsequent analyses showed that UL47 interacted with cell protein p32 in HSV-1-infected cells. Unlike in mock-infected cells, p32 accumulated at the nuclear rim in HSV-1-infected cells, and this p32 recruitment to the nuclear rim required UL47. p32 formed a complex(es) with HSV-1 proteins UL31, UL34, Us3, UL47, and/or ICP22 in HSV-1-infected cells. All these HSV-1 proteins were previously reported to be important for HSV-1 nuclear egress, in which nucleocapsids bud through the inner nuclear membrane (primary envelopment) and the enveloped nucleocapsids then fuse with the outer nuclear membrane (de-envelopment). Like viral proteins UL31, UL34, Us3, and UL47, p32 was detected in primary enveloped virions. p32 knockdown reduced viral replication and induced membranous invaginations adjacent to the nuclear rim containing primary enveloped virions and aberrant localization of UL31 and UL34 in punctate structures at the nuclear rim. These effects of p32 knockdown were reduced in the absence of UL47. Therefore, the effects of p32 knockdown in HSV-1 nuclear egress were similar to those of the previously reported mutation(s) in HSV-1 regulatory proteins for HSV-1 de-envelopment during viral nuclear egress. Collectively, these results suggested that p32 regulated HSV-1 de-envelopment and replication in a UL47-dependent manner. IMPORTANCEIn this study, we have obtained data suggesting that (i) the HSV-1 major virion structural protein UL47 interacted with host cell protein p32 and mediated the recruitment of p32 to the nuclear rim in HSV-1-infected cells; (ii) p32 was a component of the HSV-1 nuclear egress complex (NEC), whose core components were UL31 and UL34; and (iii) p32 regulated HSV-1 de-envelopment during viral nuclear egress. It has been reported that p32 was a component of human cytomegalovirus NEC and was required for efficient disintegration of nuclear lamina, which has been thought to facilitate HSV-1 primary envelopment during viral nuclear egress. Thus, p32 appeared to be a core component of herpesvirus NECs, like UL31 and UL34 homologs in other herpesviruses, and to play multiple roles in herpesvirus nuclear egress. H erpesvirus nucleocapsids are too large to traverse the nuclear lamina or cross the inner (INM) and outer (ONM) nuclear membranes through nuclear pores. Therefore, herpesviruses appear to have evolved a unique nuclear egress mechanism in which progeny nucleocapsids assembled in the nucleus acquire primary envelopes by budding through the INM into the perinuclear space (primary envelopment), the space between the INM and ONM, and enveloped nucleocapsids then fuse with the ONM to release de-enveloped nucleocapsids into the cytoplasm (de-envelopment) (1, 2). A heterodim...

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“…human immunodeficiency virus type 1 Rev (44) and Tat (43), hepatitis C virus core protein (46), EBNA-1 of Epstein-Barr virus (54), and open reading frame P of HSV (55). The intracellular localization and function of p32 have been demonstrated primarily as a mitochondrial membrane protein in harakiri-mediated apoptosis (42), a mitochondrial antiviral signaling protein-interacting protein in RNAinduced retinoic acid-inducible gene I signaling (35), an interactor of splicing factor SF2/alternative splicing factor for RNA splicing (41), and an RNA-interacting protein for the translation of mitochondrial RNA (56). To date, the only viral kinase reported to associate with intracellular p32 is human CMV pUL97, a kinase that phosphorylates nuclear lamina at the inner nuclear membrane (45).…”

Section: Discussionmentioning

confidence: 99%

p32 Is a Novel Target for Viral Protein ICP34.5 of Herpes Simplex Virus Type 1 and Facilitates Viral Nuclear Egress

Wang

Yang

et al. 2014

Journal of Biological Chemistry

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p32/gC1qR is indispensable for fetal development and mitochondrial translation: importance of its RNA-binding ability

Cited by 139 publications

References 55 publications

Proteomic Analysis of the Multimeric Nuclear Egress Complex of Human Cytomegalovirus

Proteomic Analysis of the Multimeric Nuclear Egress Complex of Human Cytomegalovirus

Role of Host Cell p32 in Herpes Simplex Virus 1 De-Envelopment during Viral Nuclear Egress

p32 Is a Novel Target for Viral Protein ICP34.5 of Herpes Simplex Virus Type 1 and Facilitates Viral Nuclear Egress

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