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Related Experiment Videos

Structure-function analysis of the human papillomavirus type 16 E7 oncoprotein.

W C Phelps1, K Münger, C L Yee

  • 1Division of Virology, Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709.

Journal of Virology
|April 1, 1992
PubMed
Summary

Human papillomavirus type 16 E7 protein’s transforming and trans-activating domains overlap, requiring retinoblastoma protein (pRB) binding for function. Separable functions of E7 indicate distinct roles in cellular transformation and gene regulation.

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Area of Science:

  • Molecular Biology
  • Oncogenesis
  • Virology

Background:

  • Human papillomavirus type 16 (HPV16) E7 protein is a nuclear phosphoprotein with functions similar to adenovirus E1A and papovavirus T antigens.
  • E7 protein is known to cooperate with ras oncogenes, transactivate promoters, and affect growth factor signaling, potentially through interaction with the retinoblastoma tumor suppressor protein (pRB).

Purpose of the Study:

  • To investigate the functional domains of the HPV16 E7 protein.
  • To determine the role of pRB association in E7's transforming and trans-activating activities.
  • To elucidate the relationship between E7's cellular transformation and trans activation functions.

Main Methods:

  • Construction and analysis of site-specific mutants of the HPV16 E7 gene.

Related Experiment Videos

  • Assessment of mutant E7 proteins for intracellular stability, ras cooperativity, and transcriptional trans activation.
  • Evaluation of pRB association and phosphorylation status of E7 mutants.
  • Main Results:

    • The transforming and trans-activating domains of E7 significantly overlap within a region analogous to adenovirus E1A conserved region 2.
    • pRB binding is essential for both the transforming and trans-activating functions of E7.
    • Deletion of sequences in conserved region 1 abolished cellular transformation but only marginally affected trans activation.

    Conclusions:

    • E7 protein's cellular transformation and trans activation functions are interrelated but separable.
    • pRB binding is a critical determinant for E7's oncogenic activities.
    • Specific regions of E7, particularly conserved region 1 and 2, play distinct roles in its multifaceted functions.