RNA Polymerase II subunit 3 is retained in the cytoplasm by its interaction with HCR, the psoriasis vulgaris candidate gene product

Corbi, Nicoletta; Bruno, Tiziana; Angelis, Roberta De; Padova, Monica Di; Libri, Valentina; Certo, Maria Grazia Di; Spinardi, Laura; Floridi, Aristide; Fanciulli, Maurizio; Passananti, Claudio

doi:10.1242/jcs.02545

Cited by 21 publications

(19 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The fluorescence revealed that the expression pattern of CCHCR1 consists in punctuated signals throughout the cytoplasm. This distribution is coherent with observations made in other cell lines [21], [22] and with its endogenous expression pattern [23]. The E2 protein from HPV16 displays a diffuse expression pattern primarily concentrated in the nucleus and also present in the cytoplasm as previously described [24].…”

Section: Resultssupporting

confidence: 91%

CCHCR1 Interacts Specifically with the E2 Protein of Human Papillomavirus Type 16 on a Surface Overlapping BRD4 Binding

Muller

Demeret

2014

PLoS ONE

View full text Add to dashboard Cite

The Human Papillomavirus E2 proteins are key regulators of the viral life cycle, whose functions are commonly mediated through protein-protein interactions with the host cell proteome. We identified an interaction between E2 and a cellular protein called CCHCR1, which proved highly specific for the HPV16 genotype, the most prevalent in HPV-associated cancers. Further characterization of the interaction revealed that CCHCR1 binds the N-terminal alpha helices of HPV16 E2 N-terminal domain. On this domain, the CCHCR1 binding interface overlaps that of BRD4, a key mediator of E2 transcriptional activity. Consequently a physical competition occurs between the two proteins for the binding to HPV16 E2, and CCHCR1 interferes with BRD4-mediated enhancement of E2-dependent transcription. In addition, we showed that the interaction with CCHCR1 induced a massive redistribution of HPV16 E2, from a predominantly nuclear to a cytoplasmic localization in dot-like structures, where E2 perfectly co-localizes with CCHCR1. Such a cytoplasmic docking likely interferes with the nuclear functions of HPV16 E2. Upon co-expression of BRD4 and CCHCR1, E2 accumulates both in the nucleus and in the cytoplasm, indicating that for HPV16, both sub-cellular localization and transcriptional functions of E2 may depend on the proportion of both factors within the cell. We provided evidence of a strong induction of the keratinocyte differentiation marker K10 by HPV16 E2, and showed that this activation is compromised by the interaction with CCHCR1. The specific interaction described here could thus impact on the pathogenesis of HPV16. We propose that it could underlie some specific traits of HPV16 infection, such as an enhanced propensity to give rise to lesions evolving toward cancer.

show abstract

Section: Resultssupporting

confidence: 91%

CCHCR1 Interacts Specifically with the E2 Protein of Human Papillomavirus Type 16 on a Surface Overlapping BRD4 Binding

Muller

Demeret

2014

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Of an estimated 2.5×10 6 transformants, 30 clones proliferated on media lacking histidine and adenine as well as stained positive for β-galactosidase. Several clones were isolated for further characterisation [6], [9]–[10] and the clone encoding for the ubiquitous eukaryotic translation elongation factor 1 gamma subunit (eEF1γ) (fig. 1B) was selected for further study.…”

Section: Resultsmentioning

confidence: 99%

“…HeLa cells were co-transfected with myc-eEF1γ and a series of RPB3 deletion mutants fused to the EGFP protein (fig. 2A) [10]. Immunoprecipitation was performed with an anti-myc monoclonal antibody and analysed by western blot using an anti-EGFP monoclonal antibody.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The eEF1γ Subunit Contacts RNA Polymerase II and Binds Vimentin Promoter Region

et al. 2010

Self Cite

View full text Add to dashboard Cite

Here, we show that the eukaryotic translation elongation factor 1 gamma (eEF1γ) physically interacts with the RNA polymerase II (pol II) core subunit 3 (RPB3), both in isolation and in the context of the holo-enzyme. Importantly, eEF1γ has been recently shown to bind Vimentin mRNA. By chromatin immunoprecipitation experiments, we demonstrate, for the first time, that eEF1γ is also physically present on the genomic locus corresponding to the promoter region of human Vimentin gene. The eEF1γ depletion causes the Vimentin protein to be incorrectly compartmentalised and to severely compromise cellular shape and mitochondria localisation. We demonstrate that eEF1γ partially colocalises with the mitochondrial marker Tom20 and that eEF1γ depletion increases mitochondrial superoxide generation as well as the total levels of carbonylated proteins. Finally, we hypothesise that eEF1γ, in addition to its role in translation elongation complex, is involved in regulating Vimentin gene by contacting both pol II and the Vimentin promoter region and then shuttling/nursing the Vimentin mRNA from its gene locus to its appropriate cellular compartment for translation.

show abstract

“…A regtilator>' role forCCHCRl in transcription factor binding has been discovered recently (17). HCR transgenic mice having either the huinan non-risk HCr< allele or the psoriasis risk allele showed altered cutaneous expression profiles for several proteins known to be upregtilated in human psoriasis, such as keratins 6, 16, and 17, tenascin C. and certain SPRRs and matrix metalloproteinases (18).…”

mentioning

confidence: 99%

Clinical Associations of the Risk Alleles of HLA-Cw6 and CCHCR1*WWCC in Psoriasis

Kainu¹,

Onkamo²,

Tiala³

et al. 2007

Acta Derm Venereol

View full text Add to dashboard Cite

The PSORS1 locus is the consistently replicated genetic risk factor for psoriasis. Clinical associations with the main marker allele of PSORS1, HLA-Cw6, have been addressed in a number of studies, but clinical associations have not been used as a way to distinguish the effects of the neighbouring candidate genes in PSORS1. Our results show that HLA-Cw6 and CCHCR1 risk allele associations with clinical features of psoriasis are predictably highly similar in a Finnish nationwide cohort of 379 psoriasis patients. The clinical profiling of a small group of patients (n=34) who were HLA-Cw6- but CCHCR1*WWCC positive suggested that no great differences existed between them and HCR-Cw6- patients. HCR+ genotype (as well as Cw6+ genotype) correlated for the first time positively with female sex and, in contrast with previous studies, negatively with disease severity. Presence of psoriatic arthritis was more pronounced in HCR- psoriasis (as well as in Cw6- psoriasis). Clinical profiling may be a useful approach to distinguishing genetic effects of candidate genes even within a locus in sufficiently large cohorts.

show abstract

RNA Polymerase II subunit 3 is retained in the cytoplasm by its interaction with HCR, the psoriasis vulgaris candidate gene product

Cited by 21 publications

References 36 publications

CCHCR1 Interacts Specifically with the E2 Protein of Human Papillomavirus Type 16 on a Surface Overlapping BRD4 Binding

CCHCR1 Interacts Specifically with the E2 Protein of Human Papillomavirus Type 16 on a Surface Overlapping BRD4 Binding

The eEF1γ Subunit Contacts RNA Polymerase II and Binds Vimentin Promoter Region

Clinical Associations of the Risk Alleles of HLA-Cw6 and CCHCR1*WWCC in Psoriasis

Contact Info

Product

Resources

About