Analyses of variant human papillomavirus type-16 E5 proteins for their ability to induce mitogenesis of murine fibroblasts

<p>Abstract</p> <p>Background</p> <p>Human papillomavirus type 16 (HPV-16) E5 protein co-operates with epidermal growth factor to stimulate mitogenesis of murine fibroblasts. Currently, little is known about which viral amino acids are involved in this process. Using se...

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Main Authors: Cason John, Kell Barbara, Mant Christine A, Nath Rahul, Bible Jon M
Format: Article
Language:English
Published: BMC 2006-08-01
Series:Cancer Cell International
Online Access:http://www.cancerci.com/content/6/1/19
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author Cason John
Kell Barbara
Mant Christine A
Nath Rahul
Bible Jon M
author_facet Cason John
Kell Barbara
Mant Christine A
Nath Rahul
Bible Jon M
author_sort Cason John
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Human papillomavirus type 16 (HPV-16) E5 protein co-operates with epidermal growth factor to stimulate mitogenesis of murine fibroblasts. Currently, little is known about which viral amino acids are involved in this process. Using sequence variants of HPV-16 E5 we have investigated their effects upon E5 transcription, cell-cycling and cell-growth of murine fibroblasts.</p> <p>Results</p> <p>We demonstrate that: (i) introduction of Thr<sup>64 </sup>into the reference E5 sequence of HPV-16 abrogates mitogenic activity: both were poorly transcribed in NIH-3T3 cells; (ii) substitution of Leu<sup>44</sup>Val<sup>65 </sup>or, Thr<sup>37</sup>Leu<sup>44</sup>Val<sup>65 </sup>into the HPV-16 E5 reference backbone resulted in high transcription in NIH-3T3 cells, enhanced cell-cycle progression and high cell-growth; and, (iii) inclusion of Tyr<sup>8 </sup>into the Leu<sup>44</sup>Val<sup>65 </sup>backbone inhibited E5 induced cell-growth and repression of p21 expression, despite high transcription levels.</p> <p>Conclusion</p> <p>The effects of HPV-16 E5 variants upon mitosis help to explain why Leu<sup>44</sup>Val<sup>65 </sup>HPV-16 E5 variants are most prevalent in 'wild' pathogenic viral populations in the UK.</p>
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spelling doaj.art-ca9cbba4e15e4040bca5eba2fd1b39372022-12-22T01:43:25ZengBMCCancer Cell International1475-28672006-08-01611910.1186/1475-2867-6-19Analyses of variant human papillomavirus type-16 E5 proteins for their ability to induce mitogenesis of murine fibroblastsCason JohnKell BarbaraMant Christine ANath RahulBible Jon M<p>Abstract</p> <p>Background</p> <p>Human papillomavirus type 16 (HPV-16) E5 protein co-operates with epidermal growth factor to stimulate mitogenesis of murine fibroblasts. Currently, little is known about which viral amino acids are involved in this process. Using sequence variants of HPV-16 E5 we have investigated their effects upon E5 transcription, cell-cycling and cell-growth of murine fibroblasts.</p> <p>Results</p> <p>We demonstrate that: (i) introduction of Thr<sup>64 </sup>into the reference E5 sequence of HPV-16 abrogates mitogenic activity: both were poorly transcribed in NIH-3T3 cells; (ii) substitution of Leu<sup>44</sup>Val<sup>65 </sup>or, Thr<sup>37</sup>Leu<sup>44</sup>Val<sup>65 </sup>into the HPV-16 E5 reference backbone resulted in high transcription in NIH-3T3 cells, enhanced cell-cycle progression and high cell-growth; and, (iii) inclusion of Tyr<sup>8 </sup>into the Leu<sup>44</sup>Val<sup>65 </sup>backbone inhibited E5 induced cell-growth and repression of p21 expression, despite high transcription levels.</p> <p>Conclusion</p> <p>The effects of HPV-16 E5 variants upon mitosis help to explain why Leu<sup>44</sup>Val<sup>65 </sup>HPV-16 E5 variants are most prevalent in 'wild' pathogenic viral populations in the UK.</p>http://www.cancerci.com/content/6/1/19
spellingShingle Cason John
Kell Barbara
Mant Christine A
Nath Rahul
Bible Jon M
Analyses of variant human papillomavirus type-16 E5 proteins for their ability to induce mitogenesis of murine fibroblasts
Cancer Cell International
title Analyses of variant human papillomavirus type-16 E5 proteins for their ability to induce mitogenesis of murine fibroblasts
title_full Analyses of variant human papillomavirus type-16 E5 proteins for their ability to induce mitogenesis of murine fibroblasts
title_fullStr Analyses of variant human papillomavirus type-16 E5 proteins for their ability to induce mitogenesis of murine fibroblasts
title_full_unstemmed Analyses of variant human papillomavirus type-16 E5 proteins for their ability to induce mitogenesis of murine fibroblasts
title_short Analyses of variant human papillomavirus type-16 E5 proteins for their ability to induce mitogenesis of murine fibroblasts
title_sort analyses of variant human papillomavirus type 16 e5 proteins for their ability to induce mitogenesis of murine fibroblasts
url http://www.cancerci.com/content/6/1/19
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