RHOBTB2 binds interacting proteins at the endosome membrane

Stable Identifier
R-HSA-9018787
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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RHOBTB2, like the other RHOBTB family member, RHOBTB1, and the divergent RHOBTB3 which does not belong to the RHO superfamily, binds CUL3 (cullin-3) (Berthold et al. 2008), a core component of BTB-CUL3-RBX1 E3 ubiquitin ligase complexes. Binding of GTP to RHOBTB2, facilitated by the HSP90 chaperone complex, enables binding of RHOBTB2 to CUL3 (Manjarrez et al. 2014). RHOBTB2 is thought to act as the regulatory BTB component of the BTB-CUL3-RBX1 complex by recruiting target proteins for ubiquitination and subsequent proteasome-mediated degradation (Wilkins et al. 2004). RHOBTB2 is a substrate adaptor for Musashi 2 (MSI2), targeting it to CUL3 complexes for ubiquitination and proteasomal degradation, thus suppressing tumorigenesis (Choi et al. 2017).

The following candidate RHOBTB2 interactors have been discovered in the high throughput screen by Bagci et al. 2020:
ACTG1 (Bagci et al. 2020)
ACTN1 (Bagci et al. 2020)
CCT2 (Bagci et al. 2020)
CCT6A (Bagci et al. 2020)
CCT7 (Bagci et al. 2020)
DBN1 (Bagci et al. 2020)
DDX39B (Bagci et al. 2020)
HNRNPC (Bagci et al. 2020)
MYO6 (Bagci et al. 2020)
PHIP (Bagci et al. 2020)
RBMX (Bagci et al. 2020)
SRRM1 (Bagci et al. 2020)
STK38 (Bagci et al. 2020)
TMOD3 (Bagci et al. 2020)
TRA2B (Bagci et al. 2020)
TWF1 (Bagci et al. 2020)
TXNL1 (Bagci et al. 2020).
Some of these interactors are part of the CCT chaperone complex (CCT2, CCT6A and CCT7), some are related to the actin cytoskeleton (ACTG1, ACTN1, DBN1, MYO6, TMOD3 and TWF1), or RNA splicing and export (DDX39B, HNRNPC, RBMX and SRRM1).

Literature References
PubMed ID Title Journal Year
18835386 Characterization of RhoBTB-dependent Cul3 ubiquitin ligase complexes--evidence for an autoregulatory mechanism

Furukawa, M, Miura, Y, Schenkova, K, Berthold, J, Ramos, S, Rivero, F, Aspenström, P

Exp. Cell Res. 2008
31871319 Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms

Tran, V, Gingras, AC, Elkholi, IE, Robert, A, Boulais, J, Faubert, D, Dubé, N, Hipfner, DR, Cote, JF, Lin, ZY, Bagci, H, Sriskandarajah, N, Thibault, MP

Nat. Cell Biol. 2020
15107402 RhoBTB2 is a substrate of the mammalian Cul3 ubiquitin ligase complex

Ping, Q, Wilkins, A, Carpenter, CL

Genes Dev. 2004
24608665 Hsp90-dependent assembly of the DBC2/RhoBTB2-Cullin3 E3-ligase complex

Prince, T, Matts, RL, Manjarrez, JR, Sun, L

PLoS ONE 2014
27941885 DBC2/RhoBTB2 functions as a tumor suppressor protein via Musashi-2 ubiquitination in breast cancer

An, S, An, IS, Choi, YM, Lee, JH, Kim, KB, Chun, YK, Bae, S

Oncogene 2017
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