Merkel Cell Polyomavirus Small T Antigen Induces DNA Damage Response.
Intervirology
; 62(2): 96-100, 2019.
Article
de En
| MEDLINE
| ID: mdl-31401636
ABSTRACT
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine cancer of the skin with high rates of metastasis and mortality. Besides well-established factors including genetic mutations and UV-induced DNA damage in Merkel cell carcinogenesis, the recent discovery of the Merkel cell polyomavirus (MCPyV) has shed light on the viral etiology of MCC. In the current study, we provide novel evidence that MCPyV small T (sT) antigen induces the DNA damage response (DDR) pathway. Our data show that in human MCC cells, the presence of MCPyV is associated with hyperphosphorylation of histone H2AX, a marker for DNA damage. We observed that overexpression of MCPyV sT antigen induced the phosphorylation of histone H2AX as well as the activation of ataxia telangiectasia mutant (ATM), an upstream kinase important for H2AX phosphorylation. Moreover, we observed that MCPyV sT expression also induced the hyperphosphorylation of other ATM downstream molecules (including 53BP1 and CHK2) as well as the hypermethylation of histone 3 and histone 4. These findings disclose a novel link between MCPyV sT and the DDR pathway in MCC. Given that measurement of DDR is clinically useful for evaluating treatment response to radio- and chemotherapy, our findings warrant further investigation to evaluate the potential implications of this pathway for MCC management.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Altération de l'ADN
/
Carcinome à cellules de Merkel
/
Expression des gènes
/
Polyomavirus des cellules de Merkel
/
Antigènes des virus oncogènes
Limites:
Humans
Langue:
En
Journal:
Intervirology
Année:
2019
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique