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Updated: May 27, 2026
13:56
A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions
Published on: July 18, 2013
Cutaneous HPV23 E6 prevents p53 phosphorylation through interaction with HIPK2
Dorothea Muschik1, Ilona Braspenning-Wesch, Eggert Stockfleth
1Viral Skin Carcinogenesis Group, Division Viral Transformation Mechanisms, German Cancer Research Center (DKFZ), DKFZ-Charité, Heidelberg, Germany.
Plos One
|November 24, 2011
Summary
Cutaneous human papillomavirus (HPV) type 23 E6 protein interferes with Homeodomain-interacting protein kinase 2 (HIPK2) function. This interaction prevents UV-induced apoptosis, potentially promoting skin cancer development.
Area of Science:
- Oncology
- Virology
- Dermatology
Background:
- Ultraviolet (UV) radiation is a primary cause of skin cancer.
- Beta-genus cutaneotropic human papillomaviruses (HPV) are implicated as co-factors in cutaneous squamous cell carcinoma.
- Homeodomain-interacting protein kinase 2 (HIPK2) acts as a tumor suppressor in skin, stabilized by UV damage and regulating apoptosis via p53 phosphorylation.
Purpose of the Study:
- To investigate the interaction between cutaneous HPV23 E6 protein and HIPK2.
- To determine the functional consequences of this interaction on p53 phosphorylation and apoptosis evasion in the context of UV damage.
Main Methods:
- In vitro and in vivo interaction assays between HPV23 E6 and HIPK2.
- Co-localization studies of HPV23 E6 and HIPK2 in nuclear bodies upon UVB exposure.
- Analysis of HIPK2/p53 complex dissociation and p53 Ser 46 phosphorylation levels.
Main Results:
- HPV23 E6 directly interacts with HIPK2 both in vitro and in vivo.
- HPV23 E6 co-localizes with HIPK2 in nuclear bodies after significant UVB exposure.
- HPV23 E6 inhibits HIPK2-mediated p53 Ser 46 phosphorylation by disrupting the HIPK2/p53 complex, leading to apoptosis evasion.
Conclusions:
- Cutaneous HPV23 E6 antagonizes HIPK2's tumor-suppressive function by preventing p53 phosphorylation.
- This mechanism may facilitate the survival of UV-damaged keratinocytes, contributing to skin carcinogenesis.
- Targeting the HPV23 E6-HIPK2 interaction could offer a novel strategy for skin cancer prevention or treatment.
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