multistep skin carcinogenesis assays were performed with mice with keratinocyte - specific deletion of the cnb1 gene ( cnb1xk5-crepr1)3 in parallel with cre - negative controls ( cnb1 ) .
detailed conditions for these assays as well as chromatin immunoprecipitation , immunoblotting , immunofluorescence , senescence -galactosidase staining , biotinylated dna pull down assays , and sorting can be found in the method section and supplementary figure legends .
 calcineurin inhibitors such as cyclosporin a ( csa ) are the mainstay of immunosuppressive treatment for organ transplant recipients . 
 squamous cell carcinoma ( scc ) of the skin is a major complication of treatment with these drugs , with a 65100 fold higher risk than in the normal population1 . 
 by contrast , the incidence of basal cell carcinoma ( bcc ) , the other major keratinocyte - derived tumour of the skin , of melanoma and of internal malignancies increases to a significantly lesser extent 1 . here 
 we report that genetic and pharmacological suppression of calcineurin / nfat function promotes tumour formation in mouse skin and in xenografts , in immune compromised mice , of h - rasv12 expressing primary human keratinocytes or keratinocyte - derived scc cells . 
 calcineurin / nfat inhibition counteracts p53-dependent cancer cell senescence thereby increasing tumourigenic potential . 
 atf3 , a member of the  enlarged  
 ap-1 family , is selectively induced by calcineurin / nfat inhibition , both under experimental conditions and in clinically occurring tumours , and increased atf3 expression accounts for suppression of p53-dependent senescence and enhanced tumourigenic potential . 
 thus , intact calcineurin / nfat signalling is critically required for p53 and senescence - associated mechanisms that protect against skin squamous cancer development . 
Methods summary
Supplementary Material