Regulation of cell cycle progression and apoptosis by the papillomavirus E6 oncogene.
Infection with human papillomaviruses (HPV) is strongly associated with the development of cervical cancer. The HPV E6 gene is essential for the oncogenic potential of HPV. E6 abrogates multiple cell cycle checkpoints and modulates apoptosis. Loss of cell cycle checkpoints contributes to genomic instability, a hallmark of cancer cells. Cancer cells also show reduced propensity for apoptotic cell death. Inactivation of the tumor suppressor p53 by E6 is an important mechanism by which E6 promotes cell growth. The molecular basis for apoptosis modulation by E6 is poorly understood. Although it is expected that inactivation of p53 by E6 should lead to a reduction in cellular apoptosis, numerous studies showed that E6 could in fact sensitize cells to apoptosis. In this article, we present an overview of observations and current understanding of the molecular basis for E6-induced cell proliferation and apoptosis.
Fan
Xueli
X
Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605-2324, USA.
Chen
Jason J
JJ
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology*; D049109:Cell Proliferation; D005260:Female; D042822:Genomic Instability; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D027383:Papillomaviridae / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*
C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53