RRAD gene expression

Stable Identifier
R-HSA-9613219
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
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

RRAD (Ras associated with diabetes) is a small GTP-binding member of the RAS superfaily that was originally as being overexpressed in skeletal muscle of people with type II diabetes (Reynet and Kahn, 1993; Zhu et al, 1995). RRAD has roles in cardiac regulation, and contributes to glucose metabolism and tumor metastasis through interaction with NME1 (nucleoside diphosphate kinase A) (Chang et al, 2007; Wang et al, 2010; Zhu et al, 1999; Tseng et al, 2001). In addition, RRAD contributes to Schwann cell development and myelination by modulating the RHO ROCK pathway (Ward et al, 2002; Yamauchi et al, 2004; Melendez-Vasquez et al, 2004). RRAD gene expression is positively regulated upon binding of EGR1 or EGR2 to their cognate sites in the promoter, while EGR-dependent recruitment of NAB proteins leads to EGR-mediated repression through the recruitment of chromatin remodellers and histone deacetylase complexes (Svaren et al, 2000; Mager et al, 2008). RRAD expression is repressed in Schwann cells during myelination and is upregulated in NAB knockout mice, implicating NAB proteins as negative regulators of RRAD expression (Verheijen et al, 2003; Mager et al, 2008; Desmazières et al, 2008). It is worth noting, however, that a number of genes required for Schwann cell differentiation and myelination are activated by EGR:NAB complexes at their promoters (Le et al, 2005).

Literature References
PubMed ID Title Journal Year
16136673 Nab proteins are essential for peripheral nervous system myelination

Le, N, Nagarajan, R, Wang, JY, Svaren, J, LaPash, C, Araki, T, Schmidt, RE, Milbrandt, J

Nat. Neurosci. 2005
8248782 Rad: a member of the Ras family overexpressed in muscle of type II diabetic humans

Reynet, C, Kahn, CR

Science 1993
7876254 Characterization of Rad, a new member of Ras/GTPase superfamily, and its regulation by a unique GTPase-activating protein (GAP)-like activity

Zhu, J, Reynet, C, Caldwell, JS, Kahn, CR

J. Biol. Chem. 1995
18456662 Active gene repression by the Egr2.NAB complex during peripheral nerve myelination

Mager, GM, Ward, RM, Srinivasan, R, Jang, SW, Wrabetz, L, Svaren, J

J. Biol. Chem. 2008
14522948 Local regulation of fat metabolism in peripheral nerves

Verheijen, MH, Chrast, R, Burrola, P, Lemke, G

Genes Dev. 2003
10611312 Interaction of the Ras-related protein associated with diabetes rad and the putative tumor metastasis suppressor NM23 provides a novel mechanism of GTPase regulation

Zhu, J, Tseng, YH, Kantor, JD, Rhodes, CJ, Zetter, BR, Moyers, JS, Kahn, CR

Proc. Natl. Acad. Sci. U.S.A. 1999
19926875 Rad as a novel regulator of excitation-contraction coupling and beta-adrenergic signaling in heart

Wang, G, Zhu, X, Xie, W, Han, P, Li, K, Sun, Z, Wang, Y, Chen, C, Song, R, Cao, C, Zhang, J, Wu, C, Liu, J, Cheng, H

Circ. Res. 2010
18056528 Rad GTPase deficiency leads to cardiac hypertrophy

Chang, L, Zhang, J, Tseng, YH, Xie, CQ, Ilany, J, Brüning, JC, Sun, Z, Zhu, X, Cui, T, Youker, KA, Yang, Q, Day, SM, Kahn, CR, Chen, YE

Circulation 2007
15102911 Rho kinase regulates schwann cell myelination and formation of associated axonal domains

Melendez-Vasquez, CV, Einheber, S, Salzer, JL

J. Neurosci. 2004
11956230 The GTP binding proteins Gem and Rad are negative regulators of the Rho-Rho kinase pathway

Ward, Y, Yap, SF, Ravichandran, V, Matsumura, F, Ito, M, Spinelli, B, Kelly, K

J. Cell Biol. 2002
10984481 EGR1 target genes in prostate carcinoma cells identified by microarray analysis

Svaren, J, Ehrig, T, Abdulkadir, SA, Ehrengruber, MU, Watson, MA, Milbrandt, J

J. Biol. Chem. 2000
15161978 Neurotrophins regulate Schwann cell migration by activating divergent signaling pathways dependent on Rho GTPases

Yamauchi, J, Chan, JR, Shooter, EM

Proc. Natl. Acad. Sci. U.S.A. 2004
18524893 Disruption of Krox20-Nab interaction in the mouse leads to peripheral neuropathy with biphasic evolution

Desmazières, A, Decker, L, Vallat, JM, Charnay, P, Gilardi-Hebenstreit, P

J. Neurosci. 2008
11280768 Regulation of growth and tumorigenicity of breast cancer cells by the low molecular weight GTPase Rad and nm23

Tseng, YH, Vicent, D, Zhu, J, Niu, Y, Adeyinka, A, Moyers, JS, Watson, PH, Kahn, CR

Cancer Res. 2001
Participants
Participant Of
This event is regulated
Authored
Reviewed
Created