MITF-M-dependent DIAPH1 expression

Stable Identifier
Reaction [omitted]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
Through its direct binding and activation of DIAPH1 gene expression, MITF-M affects processes of proliferation and invasiveness in melanoma and normal melanocyte cells (Carreira et al, 2006; reviewed in Hou and Pavan, 2008; Goding and Arnheiter, 2019).
DIAPH1 is a formin protein that affects the actin cytoskeleton at least in part through RAC (Tsuji et al, 2002). Depletion of MITF in melanoma cells results in decreased expression of DIAPH1 and an aberrant F-actin organization including a rounded cell morphology that is rescued by expression of DIAPH1 (Carreira et al, 2006). High DIAPH1 levels are associated with high levels of the F-box protein SKP2, which promotes the degradation of the cell cycle inhibitor CDKN1B (p27kip1), thus stimulating cellular proliferation (Carrano et al, 1999; Tsvetkov et al, 1999; Mammoto et al, 2004). Consistent with this, depletion of MITF in melanoma cells is associated with a CDKN1B (p27kip1)-dependent cell cycle arrest (Carreira et al, 2006).
Literature References
PubMed ID Title Journal Year
10559916 SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27

Eytan, E, Hershko, A, Pagano, M, Carrano, AC

Nat Cell Biol 1999
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
12021256 ROCK and mDia1 antagonize in Rho-dependent Rac activation in Swiss 3T3 fibroblasts

Narumiya, S, Higashida, C, Ishizaki, T, Okamoto, M, Tsuji, T, Nakamoto, T, Birge, RB, Arakawa, Y, Furuyashiki, T, Hirai, H, Kimura, K

J Cell Biol 2002
31123060 MITF-the first 25 years

Arnheiter, H, Goding, CR

Genes Dev 2019
15096506 Role of RhoA, mDia, and ROCK in cell shape-dependent control of the Skp2-p27kip1 pathway and the G1/S transition

Oh, P, Huang, S, Mammoto, A, Ingber, DE, Moore, K

J Biol Chem 2004
19002157 Transcriptional and signaling regulation in neural crest stem cell-derived melanocyte development: do all roads lead to Mitf?

Pavan, WJ, Hou, L

Cell Res 2008
10375532 p27(Kip1) ubiquitination and degradation is regulated by the SCF(Skp2) complex through phosphorylated Thr187 in p27

Sun, H, Zhang, H, Tsvetkov, LM, Lee, SJ, Yeh, KH

Curr Biol 1999
This event is regulated
Cite Us!