the canine papillomavirus and gamma hpv e7 proteins use an alternative domain to bind and destabilize the retinoblastoma protein犬类乳头瘤病毒和伽马hpv e7蛋白使用另一个域绑定,也破坏了视网膜母细胞瘤蛋白.pdfVIP
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the canine papillomavirus and gamma hpv e7 proteins use an alternative domain to bind and destabilize the retinoblastoma protein犬类乳头瘤病毒和伽马hpv e7蛋白使用另一个域绑定,也破坏了视网膜母细胞瘤蛋白
The Canine Papillomavirus and Gamma HPV E7 Proteins
Use an Alternative Domain to Bind and Destabilize the
Retinoblastoma Protein
Jingang Wang, Dan Zhou, Anjali Prabhu, Richard Schlegel*, Hang Yuan
Department of Pathology, Georgetown University Medical School, Washington, D.C., United States of America
Abstract
The high-risk HPV E6 and E7 proteins cooperate to immortalize primary human cervical cells and the E7 protein can
independently transform fibroblasts in vitro, primarily due to its ability to associate with and degrade the retinoblastoma
tumor suppressor protein, pRb. The binding of E7 to pRb is mediated by a conserved Leu-X-Cys-X-Glu (LXCXE) motif in the
conserved region 2 (CR2) of E7 and this domain is both necessary and sufficient for E7/pRb association. In the current study,
we report that the E7 protein of the malignancy-associated canine papillomavirus type 2 encodes an E7 protein that has
serine substituted for cysteine in the LXCXE motif. In HPV, this substitution in E7 abrogates pRb binding and degradation.
However, despite variation at this critical site, the canine papillomavirus E7 protein still bound and degraded pRb. Even
complete deletion of the LXSXE domain of canine E7 failed to interfere with binding to pRb in vitro and in vivo. Rather, the
dominant binding site for pRb mapped to the C-terminal domain of canine E7. Finally, while the CR1 and CR2 domains of
HPV E7 are sufficient for degradation of pRb, the C-terminal region of canine E7 was also required for pRb degradation.
Screening of HPV genome sequences revealed that the LXSXE motif of the canine E7 protein was also present in the gamma
HPVs and we demonstrate that the gamma HPV-4 E7 protein also binds pRb in a similar way. It appears, therefore, that the
type 2 canine PV and gamma-type HPVs not only share similar properties with respect to tissue specificity and association
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