RGD Reference Report - RNA splicing factors regulated by HPV16 during cervical tumour progression. - Rat Genome Database

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RNA splicing factors regulated by HPV16 during cervical tumour progression.

Authors: Mole, S  McFarlane, M  Chuen-Im, T  Milligan, SG  Millan, D  Graham, SV 
Citation: Mole S, etal., J Pathol. 2009 Nov;219(3):383-91. doi: 10.1002/path.2608.
RGD ID: 11039410
Pubmed: PMID:19718710   (View Abstract at PubMed)
PMCID: PMC2779514   (View Article at PubMed Central)
DOI: DOI:10.1002/path.2608   (Journal Full-text)

The most prevalent human papillomaviruses (HPVs) causing cervical disease are the 'high-risk' HPV types 16 and 18. All papillomaviruses express a transcription factor, E2, that can regulate viral and cellular gene expression. Recently, we demonstrated high-risk HPV E2-mediated transcriptional transactivation of SF2/ASF. This essential oncoprotein is a key member of a family of proteins, the SR proteins, that regulate constitutive and alternative splicing. Tight control of RNA splicing is necessary for the production of wild-type proteins. So, aberrant expression of SR proteins is involved in the aetiology of a range of human diseases, including cancer. Here we demonstrate epithelial differentiation-specific control of SF2/ASF in HPV16-infected keratinocytes in organotypic raft culture and in low-grade cervical lesions (CIN1). Further, we demonstrate HPV16 infection/differentiation-induced up-regulation of a specific subset of SR proteins and present evidence that HPV16 E2 controls expression of SRp20, SC35 and SRp75. Using a series of cell lines that model cervical tumour progression, we show that SF2/ASF, SRp20 and SC35 are specifically up-regulated in a model of cervical tumour progression. These SR proteins are also over-expressed in high-grade cervical lesions, indicating that they may all have oncogenic functions. SR proteins could be useful biomarkers for HPV-associated disease.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cervix uteri carcinoma in situ disease_progressionIEP 11039410associated with Papillomavirus Infections and protein:altered expression:uterine cervix (human)RGD 
cervix uteri carcinoma in situ disease_progressionISOSRSF1 (Homo sapiens)11039410; 11039410associated with Papillomavirus Infections and protein:altered expression:uterine cervix (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Srsf1  (serine and arginine rich splicing factor 1)

Genes (Mus musculus)
Srsf1  (serine and arginine-rich splicing factor 1)

Genes (Homo sapiens)
SRSF1  (serine and arginine rich splicing factor 1)


Additional Information