Emerging differential roles of the pRb tumor suppressor in trichodysplasia spinulosa-associated polyomavirus and Merkel cell polyomavirus pathogeneses

Wu, JH; Simonette, Rebecca A.; Nguyen, Harrison P.; Doan, Hung Q.; Rády, Peter L.; Tyring, Stephen K.

doi:10.1016/j.jcv.2016.01.001

Cited by 8 publications

(20 citation statements)

References 16 publications

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“…Indeed, MEK‐ERK phosphorylation has also been described in the context of TSPyV sT . However, we observed key differences between TSPyV sT and mT regulation of PP2A's downstream effectors – while TSPyV sT activates c‐Jun and deactivates pRb as shown in previous studies, TSPyV mT antigen results in activation of MNK1 with no significant effect on c‐Jun or pRb as documented in the current study.…”

Section: Discussionsupporting

confidence: 71%

“…Thus, a specific function for LT antigen in the context of TS has not yet been established. In contrast to LT, several lines of evidence have implicated TSPyV sT antigen in processes that may drive cell proliferation . Of particular significance, sT antigen sequence identity overlaps completely with the first exon that encodes mT antigen (nt 5034‐3336); thus, it is not surprising that sT and mT antigen may share some mechanistic properties.…”

Section: Discussionmentioning

confidence: 99%

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Dysregulation of the MEK/ERK/MNK1 signalling cascade by middle T antigen of the trichoydsplasia spinulosa polyomavirus

Wu¹,

Narayanan

Simonette³

et al. 2017

Acad Dermatol Venereol

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Dysregulation of the MEK/ERK/MNK1 signalling cascade by middle T antigen of the trichoydsplasia spinulosa polyomavirus

Wu¹,

Narayanan

Simonette³

et al. 2017

Acad Dermatol Venereol

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“…Using immunohistochemistry applied to LT viral proteins, one study found that TSPyV LT expression occurs in close proximity to phosphorylated Rb in TS hair follicles, but it is inconclusive whether TSPyV LT is able to promote Rb hyperphosphorylation . Rather, TSPyV sT is believed to be the main driver of the inner root sheath cell hyperproliferation that is characteristic of TS . Still, the applicability of TSPyV sT for diagnostic, prognostic and treatment purposes remains unknown .…”

Section: Trichodysplasia Spinulosa‐associated Polyomavirusmentioning

confidence: 99%

“…Rather, TSPyV sT is believed to be the main driver of the inner root sheath cell hyperproliferation that is characteristic of TS . Still, the applicability of TSPyV sT for diagnostic, prognostic and treatment purposes remains unknown . Figure is a simplified illustration of the proposed molecular mechanism of TSPyV sT. Lastly, TSPyV tiny T and ALTO are encoded by the splice products T3 and T4, respectively .…”

Section: Trichodysplasia Spinulosa‐associated Polyomavirusmentioning

confidence: 99%

“…TSPyV sT binds to protein phosphatase 2A (PP2A), disabling its tumour‐suppressor function and rendering PP2A incapable of dephosphorylating the downstream targets of the mitogen‐activated protein kinase (MAPK) pathway. These targets include extracellular signal‐regulated kinase (ERK), MAPK/ERK [MAPK kinase (MEK)], MAPK‐interacting serine/threonine protein kinase 1 and c‐Jun (Jun proto‐oncogene) . TSPyV sT also mediates the inactivation of pRb (retinoblastoma protein), which normally inhibits cell growth and proliferation by binding to E2 transcription factor (E2F) to prevent progression from the G 1 ‐phase to the S‐phase of the cell cycle .…”

Section: Trichodysplasia Spinulosa‐associated Polyomavirusmentioning

confidence: 99%

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Polyomaviruses of the skin: integrating molecular and clinical advances in an emerging class of viruses

Tran

Rády²,

Dao

et al. 2019

Br J Dermatol

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Summary Background Human polyomaviruses (HPyVs) are small, nonenveloped, double‐stranded DNA viruses that express tumour antigen proteins. Fourteen species of polyomaviruses have been discovered in humans, and since the 2008 discovery of the first cutaneous polyomavirus – Merkel cell polyomavirus (MCPyV) – six more species have been detected in the skin: trichodysplasia spinulosa‐associated polyomavirus (TSPyV), HPyV6, HPyV7, HPyV9, HPyV10 and HPyV13. Of these cutaneous species, only MCPyV, TSPyV, HPyV6 and HPyV7 have been definitively associated with diseases of the skin, most commonly in immunocompromised individuals. MCPyV is a predominant aetiology in Merkel cell carcinomas. TSPyV is one of the aetiological factors of trichodysplasia spinulosa. HPyV6 and HPyV7 have been recently linked to pruritic skin eruptions. The roles of HPyV9, HPyV10 and HPyV13 in pathogenesis, if any, are still unknown, but their molecular features have provided some insight into their functional biology. Results In this review, we summarize the known molecular mechanisms, clinical presentation and targeted therapies of each of the eight cutaneous HPyVs. Conclusions We hope that heightened awareness and clinical recognition of HPyVs will lead to increased reports of HPyV‐associated diseases and, consequently, a more robust understanding of how to diagnose and treat these conditions.

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Molecular mechanisms supporting a pathogenic role for human polyomavirus 6 small T antigen: Protein phosphatase 2A targeting and MAPK cascade activation

Simonette²,

Nguyen

et al. 2016

Journal of Medical Virology

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BRAF inhibitors are highly effective therapies in treating a subset of melanomas but are associated with induction of secondary cutaneous squamous cell carcinoma (cSCC). Recently, Human Polyomavirus 6 (HPyV6) was found to actively express viral proteins in BRAF inhibitor-induced cSCCs; however, the specific cellular mechanisms by which HPyV6 may facilitate neoplastic cell growth require further investigation. The current study describes a novel pathogenic mechanism of action for HPyV6 small tumor (sT) antigen which involves binding to protein phosphatase 2A (PP2A) via its WFG motif and zinc binding sites. Our findings demonstrate an important role of HPyV6 sT for activation of PP2A's downstream oncogenic pathways (MEK/ERK/c-Jun), which may underlie the pathogenesis of BRAF inhibitor-induced neoplasms. J. Med. Virol. 89:742-747, 2017. © 2016 Wiley Periodicals, Inc.

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Emerging differential roles of the pRb tumor suppressor in trichodysplasia spinulosa-associated polyomavirus and Merkel cell polyomavirus pathogeneses

Cited by 8 publications

References 16 publications

Dysregulation of the MEK/ERK/MNK1 signalling cascade by middle T antigen of the trichoydsplasia spinulosa polyomavirus

Dysregulation of the MEK/ERK/MNK1 signalling cascade by middle T antigen of the trichoydsplasia spinulosa polyomavirus

Polyomaviruses of the skin: integrating molecular and clinical advances in an emerging class of viruses

Molecular mechanisms supporting a pathogenic role for human polyomavirus 6 small T antigen: Protein phosphatase 2A targeting and MAPK cascade activation

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