NFX1-123 and poly(A) binding proteins synergistically augment activation of telomerase in human papillomavirus type 16 E6-expressing cells.

NFX1-123 and poly(A) binding proteins synergistically augment activation of telomerase in human papillomavirus type 16 E6-expressing cells. Research Abstract Details 

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NFX1-123 and poly(A) binding proteins synergistically augment activation of telomerase in human papillomavirus type 16 E6-expressing cells. Abstract Text:

Rachel A Katzenellenbogen,Erin M Egelkrout,Portia Vliet-Gregg,Lindy C Gewin,Philip R Gafken,Denise A Galloway,

Overcoming senescence signals in somatic cells is critical to cellular immortalization and carcinogenesis. High-risk human papillomavirus (HPV) can immortalize epithelial cells in culture through degradation of the retinoblastoma protein by HPV E7 and activation of hTERT transcription, the catalytic subunit of telomerase, by the heterodimer HPV E6/E6-associated protein (E6AP). Recent work in our laboratory identified a novel repressor of hTERT transcription, NFX1-91, which is targeted for ubiquitin-mediated degradation by HPV type 16 (HPV16) E6/E6AP. In contrast, NFX1-123, a splice variant NFX1, increased expression from an hTERT promoter that was activated by HPV16 E6/E6AP. Here, we show that HPV16 E6 bound both NFX1-91 and NFX1-123 through the common central domain of NFX1 in the absence of E6AP. NFX1-123 positively regulated hTERT expression, as its knockdown decreased hTERT mRNA levels and telomerase activity and its overexpression increased telomerase activity. We identified new protein partners of NFX1-123, including several cytoplasmic poly(A) binding proteins (PABPCs) that interacted with NFX1-123 through its N-terminal PAM2 motif, a protein domain characteristic of other PABPC protein partners. Furthermore, NFX1-123 and PABPCs together had a synergistic stimulatory effect on hTERT-regulated reporter assays. The data suggest that NFX1-123 is integral to hTERT regulation in HPV16 E6-expressing epithelial cells and that the interaction between NFX1-123 and PABPCs is critical to hTERT activity.

NFX1-123 and poly(A) binding proteins synergistically augment activation of telomerase in human papillomavirus type 16 E6-expressing cells. Publishing Authors By Initials

RA Katzenellenbogen,EM Egelkrout,P Vliet-Gregg,LC Gewin,PR Gafken,DA Galloway,

For similar enzymes and coenzymes: enzymes: transferases: phosphotransferases: nucleotidyltransferases: dna nucleotidyltransferases: dna-directed dna polymerase: rna-directed dna polymerase: telomerase research abstracts see: enzymes and coenzymes: enzymes: transferases: phosphotransferases: nucleotidyltransferases: dna nucleotidyltransferases: dna-directed dna polymerase: rna-directed dna polymerase: telomerase research

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NFX1-123 and poly(A) binding proteins synergistically augment activation of telomerase in human papillomavirus type 16 E6-expressing cells. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of virology

VOLUME: 81

Page Numbers: 3786-96

Journal Abbreviation: J. Virol.

ISSN: 0022-538X

DAY: 31

MONTH: 01

YEAR: 2007

NFX1-123 and poly(A) binding proteins synergistically augment activation of telomerase in human papillomavirus type 16 E6-expressing cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 113724

NFX1-123 and poly(A) binding proteins synergistically augment activation of telomerase in human papillomavirus type 16 E6-expressing cells. Keywords Mesh Terms:

KEYWORDS: Telomerase

MESH TERMS: metabolism

Chemical & Substance for Abstract: NFX1-123 and poly(A) binding proteins synergistically augment activation of telomerase in human papillomavirus type 16 E6-expressing cells. Information

Substance Name: Telomerase

Registry Number: EC 2.7.7.49

Grant and Affiliation Information for NFX1-123 and poly(A) binding proteins synergistically augment activation of telomerase in human papillomavirus type 16 E6-expressing cells.

AFFILIATION: Fred Hutchinson Cancer Research Center, and Department of Pediatrics, University of Washington, Seattle, WA 98109, USA. rkatzen@u.washington.edu

Country: United States

AGENCY: United States NCI

GRANT: T32 CA09229

ACRONYM: CA

MEDLINETA: J Virol

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