Indeed, silencing RFC4 caused a remarkable increase in K48-linked polyubiquitination of NICD1, and thus overexpressing RFC4 markedly prolonged, whereas silencing RFC4 greatly shortened the half-lives of NICD1 proteins in both various NSCLC cell lines and primary NSCLC cells (Fig. 4c, d and Supplementary Fig. 6b, c). Here, RFC4 is linked to non-small cell lung carcinoma.