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HPV16 E5 affects the KGFR/FGFR2b-mediated epithelial growth through alteration of the receptor expression, signaling and endocytic traffic

Belleudi, F, Leone, L, Purpura, V, Cannella, F, Scrofani, C, Torrisi, M R·2011·Oncogene
DOI 10.1038/onc.2011.203
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Abstract

The E5 oncoprotein of the human papillomavirus type 16 (HPV16 E5) cooperates in cervical carcinogenesis and in epithelial transformation deregulating cell growth, survival and differentiation through the modulation of growth factor receptors. Among the epithelial receptor tyrosine kinases, the keratinocyte growth factor receptor/fibroblast growth factor receptor 2b (KGFR/FGFR2b) is a major paracrine mediator of epithelial homeostasis and appears to have an unique and unusual role in epithelial tissues, exerting a tumor-suppressive function in vitro and in vivo. With the aim to better elucidate the molecular events involved in the pathological activity of 16E5, we investigated if the viral protein would be able to affect the KGFR expression, signaling and turnover by interference with its degradative and recycling endocytic pathways. Quantitative reverse transcriptase-PCR and biochemical approaches on human keratinocytes transfected with 16E5-HA showed that E5 protein is able to induce KGFR down-modulation at both transcript and protein levels. Immunofluorescence microscopy in double-transfected cells expressing both E5 and KGFR revealed that the viral protein alters the receptor endocytic trafficking and triggers its endosomal sorting to the indirect juxtanuclear recycling pathway. The shift from lysosomal degradation to recycling at the plasma membrane correlates with a reduced phosphorylation of the fibroblast growth factor receptor substrate-2α tyrosine 196, the major dock…

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Metadata

Authors
Belleudi, F., Leone, L., Purpura, V, Cannella, F., Scrofani, C., & Torrisi, M. R.
Venue
Oncogene
Publisher
Springer Science and Business Media LLC
Published
2011-05-30
Volume
30
Issue
50
Pages
4963-4976
ISSN
  • 0950-9232
  • 1476-5594
DOI
10.1038/onc.2011.203
Cited by
37
References
0
Language
en
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CoChat. (2026). Citation check: HPV16 E5 affects the KGFR/FGFR2b-mediated epithelial growth through alteration of the receptor expression, signaling and endocytic traffic. https://app.cochat.ai/papers/10.1038/onc.2011.203
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Belleudi, F., Leone, L., Purpura, V, Cannella, F., Scrofani, C., & Torrisi, M. R. (2011). HPV16 E5 affects the KGFR/FGFR2b-mediated epithelial growth through alteration of the receptor expression, signaling and endocytic traffic. Oncogene. https://doi.org/10.1038/onc.2011.203