Regulation of MITF-M-dependent genes involved in cell cycle and proliferation

Depending on the overall level of activity, MITF may have a proliferative or antiproliferative role. In what has been termed a rheostat model of action, low-levels of MITF activity are associated with dedifferentiation, invasion, p27kip (CDKN1B)-dependent cell cycle arrest and low proliferative rates, while higher MITF activity drive proliferation by upregulation of cell-cycle and mitotic genes such as CDK2, CCNB1, CCND1, MET, PLK1, CENPA and NDC80. At even higher MITF levels, cell-cycle is arrested by virtue of expression of p21 (CDKN1A) and p16 (CDKN2A) (Carreira et al, 2005; Loercher et al, 2005; reviewed in Goding and Arnheiter, 2019). This rheostat model of MITF activity and target gene expression can also be used to describe the role of MITF in the development of melanoma, with activation of different groups of target genes driving proliferation and invasion without activation of pigmentation genes (Hoek and Goding, 2010; reviewed in Mort et al, 2015; White and Zon, 2008).

Summary from Reactome (R-HSA-9825892), read 2026-09-23.