The human papillomavirus type 58 E7 oncoprotein modulates cell cycle regulatory proteins and abrogates cell cycle checkpoints.
HPV type 58 (HPV-58) is the third most common HPV type in cervical cancer from Eastern Asia, yet little is known about how it promotes carcinogenesis. In this study, we demonstrate that HPV-58 E7 significantly promoted the proliferation and extended the lifespan of primary human keratinocytes (PHKs). HPV-58 E7 abrogated the G1 and the postmitotic checkpoints, although less efficiently than HPV-16 E7. Consistent with these observations, HPV-58 E7 down-regulated the cellular tumor suppressor pRb to a lesser extent than HPV-16 E7. Similar to HPV-16 E7 expressing PHKs, Cdk2 remained active in HPV-58 E7 expressing PHKs despite the presence of elevated levels of p53 and p21. Interestingly, HPV-58 E7 down-regulated p130 more efficiently than HPV-16 E7. Our study demonstrates a correlation between the ability of down-regulating pRb/p130 and abrogating cell cycle checkpoints by HPV-58 E7, which also correlates with the biological risks of cervical cancer progression associated with HPV-58 infection.
Zhang
Weifang
W
Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
Li
Jing
J
Kanginakudru
Sriramana
S
Zhao
Weiming
W
Yu
Xiuping
X
Chen
Jason J
JJ
D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D050719:Crk-Associated Substrate Protein / Q000037:antagonists & inhibitors; D051357:Cyclin-Dependent Kinase 2 / Q000096:biosynthesis; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D015603:Keratinocytes / Q000821:virology; D009687:Nuclear Proteins / Q000378:metabolism*; D027383:Papillomaviridae / Q000472:pathogenicity*; D050725:Papillomavirus E7 Proteins / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors
C493841:BCAR1 protein, human; D018797:Cell Cycle Proteins; D050719:Crk-Associated Substrate Protein; D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; D050725:Papillomavirus E7 Proteins; C062521:RCC1 protein, human; D025521:Tumor Suppressor Proteins; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2