Reactome | RHOBTB2 binds interacting proteins at the endosome membrane

RHOBTB2 binds interacting proteins at the endosome membrane

Stable Identifier

R-HSA-9018787

Type

Reaction [binding]

Species

Homo sapiens

Compartment

endosome membrane, cytosol

ReviewStatus

5/5

Locations in the PathwayBrowser

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Signal Transduction (Homo sapiens)

- Signaling by Rho GTPases, Miro GTPases and RHOBTB3 (Homo sapiens)
  - Signaling by Rho GTPases (Homo sapiens)
    - RHO GTPase cycle (Homo sapiens)
      - RHOBTB GTPase Cycle (Homo sapiens)
        
        RHOBTB2 GTPase cycle (Homo sapiens)
        
        RHOBTB2 binds interacting proteins at the endosome membrane (Homo sapiens)

General

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RHOBTB2 binds interacting proteins at the endosome membrane

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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
24608665	Hsp90-dependent assembly of the DBC2/RhoBTB2-Cullin3 E3-ligase complex Prince, T, Matts, RL, Manjarrez, JR, Sun, L	PLoS ONE	2014
15107402	RhoBTB2 is a substrate of the mammalian Cul3 ubiquitin ligase complex Ping, Q, Wilkins, A, Carpenter, CL	Genes Dev.	2004
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
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
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