Oncogenic Viral Protein Interactions with p53 Family Proteins

Česká verzia

Authors: V. Brychtová; V. Hrabal; B. Vojtěšek
Authors place of work: Regionální centrum aplikované molekulární onkologie, Masarykův onkologický ústav, Brno
Published in the journal: Klin Onkol 2019; 32(Supplementum 3): 72-77
Category: Review
doi: https://doi.org/10.14735/amko20193S

Summary

Background: Cellular transformation induced by oncogenic viruses is a complex process including viral molecules, host cells and environmental factors. Viruses alone are unable to reproduce and thus they need a host to use their signalling, proteosynthetic and metabolic pathways. One target host molecule is the p53 tumour suppressor. Viral proteins functionally inactivate p53 and deregulate the expression of proteins active during apoptosis, cell proliferation and DNA damage response. Hepatitis virus B HbX protein and hepatitis virus C proteins NS2 and NS5A interact with p53 and prevent its localisation to the nucleus and thus reduce its transcriptional activity. Another mechanism lies in elevated p53 degradation caused by the BZLF1 protein of the Epstein-Barr virus, the LANA protein of the Kaposi sarcoma virus and human papilloma virus E6. The Merkel cell polyomavirus large T antigen does not interact directly with p53, however it acts through downregulation of p53 mediated transcription. The tax protein of human T cell lymphotropic virus type 1 modifies p53 posttranslationally and thus blocks its interaction with other factors of transcription machinery. Due to its tumour suppressor function and role in the maintenance of the genome integrity, the p53 protein is one of the best studied proteins. Following this, evolutionary homologues with important developmental functions p63 and p73 are intensively studied as well. Their roles in oncogenesis have not been clarified yet.

Purpose: This review describes some of their known interactions with oncogenic viral proteins.

Keywords:

p53 – viruses – viral proteins – p63 – p73 – tumorigenesis

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