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Molecular mechanisms supporting a pathogenic role for human polyomavirus 6 small T antigen: Protein phosphatase 2A

Julie H Wu1,2, Rebecca A Simonette1, Harrison P Nguyen1,2

  • 1Department of Dermatology, University of Texas Health Science Center, Houston, Texas.

Journal of Medical Virology
|September 16, 2016
PubMed

Insights

Human Polyomavirus 6 (HPyV6) small tumor antigen activates protein phosphatase 2A (PP2A), driving oncogenic pathways. This mechanism may explain how HPyV6 contributes to secondary skin cancers in BRAF inhibitor melanoma treatments.

Area of Science:

  • Oncology
  • Virology
  • Dermatology

Background:

  • BRAF inhibitors treat melanoma but can cause secondary cutaneous squamous cell carcinoma (cSCC).
  • Human Polyomavirus 6 (HPyV6) proteins are found in BRAF inhibitor-induced cSCCs.
  • The mechanism by which HPyV6 promotes neoplastic growth is unclear.

Purpose of the Study:

  • To investigate the pathogenic mechanism of HPyV6 small tumor (sT) antigen in BRAF inhibitor-induced neoplasms.
  • To elucidate the interaction between HPyV6 sT and cellular proteins involved in cancer development.

Main Methods:

  • Investigated the binding of HPyV6 sT antigen to protein phosphatase 2A (PP2A).
  • Analyzed the role of HPyV6 sT antigen's WFG motif and zinc binding sites in PP2A interaction.
  • Examined the activation of downstream oncogenic pathways (MEK/ERK/c-Jun) by HPyV6 sT-PP2A interaction.

Main Results:

  • HPyV6 sT antigen binds to PP2A via its WFG motif and zinc binding sites.
  • HPyV6 sT antigen activates PP2A.
  • Activation of PP2A by HPyV6 sT leads to the activation of downstream oncogenic pathways, including MEK/ERK/c-Jun.

Conclusions:

  • HPyV6 sT antigen plays a significant role in the pathogenesis of BRAF inhibitor-induced neoplasms.
  • The interaction between HPyV6 sT and PP2A activates oncogenic signaling pathways.
  • This study reveals a novel mechanism for HPyV6 in promoting cancer development.
Keywords:
BRAFHuman polyomavirus 6 (HPyV6)MAPKPP2Ainhibitor-induced cSCCsT antigen

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