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

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

Stable Identifier

R-HSA-9825892

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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

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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 (Carreira et al, 2006; Strub et al, 2011; McGill et al, 2006; Beuret et al, 2007; Webster et al, 2014). 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).

Literature References

PubMed ID	Title	Journal	Year
25670789	The melanocyte lineage in development and disease Jackson, IJ, Patton, EE, Mort, RL	Development	2015
18786412	Melanocytes in development, regeneration, and cancer White, RM, Zon, LI	Cell Stem Cell	2008
15716956	Mitf cooperates with Rb1 and activates p21Cip1 expression to regulate cell cycle progression Galibert, MD, Aksan, I, Carreira, S, Goodall, J, La Rocca, SA, Goding, CR, Denat, L, Larue, L	Nature	2005
15623583	MITF links differentiation with cell cycle arrest in melanocytes by transcriptional activation of INK4A Loercher, AE, Harbour, JW, Delston, RB, Tank, EM	J Cell Biol	2005
20726948	Cancer stem cells versus phenotype-switching in melanoma Goding, CR, Hoek, KS	Pigment Cell Melanoma Res	2010
31123060	MITF-the first 25 years Arnheiter, H, Goding, CR	Genes Dev	2019
21258399	Essential role of microphthalmia transcription factor for DNA replication, mitosis and genomic stability in melanoma Ye, T, Cormont, M, Keime, C, Kobi, D, Davidson, I, Le Gras, S, Giuliano, S, Bonet, C, Bertolotto, C, Ballotti, R, Strub, T	Oncogene	2011
16455654	c-Met expression is regulated by Mitf in the melanocyte lineage McGill, GG, Nishimura, EK, Haq, R, Fisher, DE	J Biol Chem	2006
17371876	Up-regulation of MET expression by alpha-melanocyte-stimulating hormone and MITF allows hepatocyte growth factor to protect melanocytes and melanoma cells from apoptosis Bertolotto, C, Picardo, M, Bille, K, Denoyelle, C, Beuret, L, Busca, R, Flori, E, Ballotti, R	J Biol Chem	2007
17182868	Mitf regulation of Dia1 controls melanoma proliferation and invasiveness Nuciforo, P, Carreira, S, Goodall, J, Rodriguez, M, Goding, CR, Denat, L, Larue, L, Testori, A, Hoek, KS	Genes Dev	2006