p32 (gC1qBP) Is a General Protein Kinase C (PKC)-binding Protein

Robles-Flores, Martha; Rendón-Huerta, Erika P.; González-Aguilar, Héctor; Mendoza‐Hernández, Guillermo; Islas, Socorro; Mendoza, Valentín; Ponce-Castañeda, M. Verónica; González‐Mariscal, Lorenza; López‐Casillas, Fernando

doi:10.1074/jbc.m109333200

Cited by 68 publications

(26 citation statements)

References 38 publications

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“…In this respect, p32 probably serves as an adaptor to bridge viral and host proteins. This notion is consistent with the observation noted in cytomegalovirus infection (48,53). Although mostly present in the cytoplasm, p32 was recruited to the nuclear rim by ICP34.5 in HSV-1-infected cells.…”

Section: Discussionsupporting

confidence: 80%

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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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Section: Discussionsupporting

confidence: 80%

“…binds to several PKC isoforms in vitro (53). Because neither p32 nor ICP34.5 is a kinase, we hypothesized that p32 may chaperone PKC to the nuclear rim along with ICP34.5.…”

Section: Pkc␦ Is Responsible For the Phosphorylation Of Lamin A/c (Sementioning

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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“…As P32 interacts with several other viral proteins such as HIV Tat (23), HIV Rev (32), or the Epstein-Barr virus protein EBNA-1 (33), it is interesting to speculate that P32 might also be involved in regulating their subcellular distribution with possible implications for the viral life cycle. Apart from viral proteins, P32 has been shown to interact with a variety of cellular proteins, including kinases such as extracellular signal-regulated kinase (ERK) and protein kinase C, which under certain conditions localize to the nucleus (34,35) or the splicing factor ASF/SF2 (30), and it is of course conceivable that the intracellular distribution of these proteins is regulated by P32. This appears highly possible, considering the localization of P32 to diverse cellular compartments, which might facilitate the traffic of P32-bound proteins between these compartments, as we have shown here for the nuclear import of U2AF26.…”

Section: Discussionmentioning

confidence: 99%

Differential Isoform Expression and Interaction with the P32 Regulatory Protein Controls the Subcellular Localization of the Splicing Factor U2AF26

Heyd

Carmo‐Fonseca

Möröy

2008

Journal of Biological Chemistry

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The U2 auxiliary factor (U2AF) is an integral part of the spliceosome that is important for the recognition of the 3 splice site. U2AF consists of a large and a small subunit, the prototypes of which are U2AF65 and U2AF35. Recent evidence suggests that several homologs of both U2AF subunits exist that are able to regulate alternative splicing. Here we have investigated the expression, intracellular localization, and nucleo-cytoplasmic shuttling of one homolog of the small U2AF subunit, U2AF26, and a splice variant lacking exon 7, U2AF26⌬E7. In contrast to the nuclear U2AF26, which displays active nucleo-cytoplasmic shuttling, U2AF26⌬E7 is localized in the cytoplasm. Our studies reveal a nuclear localization sequence in the C-terminal exons 7 and 8 of U2AF26 that differs from the known nuclear localization sequence in U2AF35. In addition, we could identify P32 as a protein that is able to interact with U2AF26 through this domain, and we demonstrate that this interaction is required for the nuclear translocation of U2AF26. Our results suggest the existence of two distinct nuclear import pathways for U2AF26 and U2AF35 that could independently control their intracellular distribution and availability to the splicing machinery. Such a mechanism could work in addition to the differential expression of U2AF homologs to contribute to the regulation of alternative splicing.With the genomes of several species being sequenced, the interest to understand the mechanisms that increase protein diversity independent of the number of protein-coding genes has risen considerably in recent years. Because of its potential to generate multiple, functionally distinct proteins from one pre-mRNA, alternative splicing is one of the mechanisms that has gained much attention in the post-genomic era (for recent reviews see Refs. 1 and 2). The decision of whether or not an exon is included in the mature mRNA is taken by the assembly of the spliceosome at a given splice site (ss), 2 which leads to the excision of the neighboring intron and inclusion of the respective exon. In the case of alternatively spliced exons, the assembly of the spliceosome is a regulated process that can either take place or not, leading to inclusion or exclusion of the exon from the final message (1).One of the early steps in spliceosome assembly is the recognition of the 3Ј ss by the heterodimeric splicing factor U2AF, which subsequently recruits the U2snRNP to the pre-mRNA (3). U2AF consists of a 35-kDa subunit that binds to the AG dinucleotide at the 3Ј splice site (4 -6) and a 65-kDa subunit that binds the adjacent polypyrimidine tract upstream of the 3Ј splice junction (7). Although the vast majority of research has been devoted to the U2AF35 and U2AF65 subunits, bioinformatic approaches have demonstrated the presence of several homologs of both U2AF subunits in mammalian genomes, some of which have been cloned and functionally tested (8 -10). Furthermore, expressed sequence tag data base searches and experimental evidence suggest that most of these subunits are...

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“…In summary, the immunofluorescence experiments are consistent with the CoIP and yeast two-hybrid analyses, suggesting a complex formation among these viral and cellular proteins. In this context, p32 appears to be an important factor for establishing the NEC due to its various protein-protein interactions with pUL50, pUL53, pUL97, PKC and LBR (Milbradt et al, 2007;Marschall et al, 2005;Mylonis et al, 2004;Storz et al, 2000;Robles-Flores et al, 2002). Additionally, the recruitment of cellular and viral protein kinases to the nuclear rim is essential for the reorganization of the nuclear lamina (Muranyi et al, 2002;Park & Baines, 2006).…”

Section: Imaging Of Protein Complex Formation At the Nuclear Laminamentioning

confidence: 99%

Cytomegaloviral proteins that associate with the nuclear lamina: components of a postulated nuclear egress complex

Milbradt

Auerochs

Sticht

et al. 2009

Journal of General Virology

149

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The nuclear egress of cytomegaloviral capsids traversing the nuclear envelope is dependent on a locally restricted destabilization of the rigid nuclear lamina. It has been suggested that the multicomponent nuclear egress complex (NEC) that is formed is comprised of both viral and cellular proteins which act to recruit lamin-phosphorylating protein kinases. Recently, we reported that the lamina-associated human cytomegalovirus-encoded proteins pUL50 and pUL53, conserved among herpesviruses, interact with each other and recruit protein kinase C (PKC) to the nuclear envelope in transfected cells. The multiple interactions of the transmembrane protein pUL50 with pUL53, PKC and cellular PKC-binding protein p32, appear crucial to the formation of the NEC. In this study, we mapped individual interaction sequence elements of pUL50 by coimmunoprecipitation analysis of deletion mutants and yeast two-hybrid studies. Amino acids 1-250 were shown to be responsible for interaction with pUL53, 100-280 for PKC and 100-358 for p32. Interestingly, p32 specifically interacted with multiple NEC components, including the kinases PKC and pUL97, thus possibly acting as an adaptor for protein recruitment to the lamin B receptor. Notably, p32 was the only protein that interacted with the lamin B receptor. Immunofluorescence studies visualized the colocalization of NEC components at the nuclear rim in coexpression studies. The data imply that a tight interaction between at least six viral and cellular proteins leads to the formation of a postulated multi-protein complex required for nuclear egress. INTRODUCTIONHuman cytomegalovirus (HCMV), a member of the bherpesvirus subfamily, is a ubiquitous, clinically important human pathogen that causes severe systemic disease in immunosuppressed hosts and prenatally infected children (Mocarski et al., 2007). As is characteristic for most DNA viruses, HCMV replicates its genome in the nucleus of the host cell. Thereafter, preformed viral capsids are packaged with genomic DNA and have to be transported to the cytoplasm for final maturation and viral release. Due to the large size of cytomegaloviral capsids (~130 nm; Chen et al., 1999), these cannot be transported through the nuclear pore complex (~40 nm; Panté & Kann, 2002). The most widely accepted model for nuclear egress of HCMV and other herpesviruses is based on a transient primary envelopment by budding through the inner nuclear membrane (Mettenleiter, 2004(Mettenleiter, , 2006Sanchez & Spector, 2002;Sampaio et al., 2005). However, before herpesvirusencoded capsids gain access to the inner nuclear membrane, the rigid proteinaceous network of the nuclear lamina provides a major obstacle. Thus, the locally restricted destabilization of the nuclear lamina is required during the viral replication process .A basic principle of the reorganization of the nuclear lamina is the recruitment of cellular and/or virus-encoded protein kinases to increase the site-specific phosphorylation of nuclear lamins and lamin-binding proteins (Dechat et al., 2008). Ce...

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p32 (gC1qBP) Is a General Protein Kinase C (PKC)-binding Protein

Cited by 68 publications

References 38 publications

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

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

Differential Isoform Expression and Interaction with the P32 Regulatory Protein Controls the Subcellular Localization of the Splicing Factor U2AF26

Cytomegaloviral proteins that associate with the nuclear lamina: components of a postulated nuclear egress complex

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