UCHL5, USP15 deubiquitinate TGFBR1

Stable Identifier
R-HSA-2179291
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol, extracellular region, plasma membrane
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UCHL5, USP15 deubiquitinate TGFBR1
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Ubiquitin C-terminal hydrolase UCHL5 (UCH37) deubiquitinates TGFBR1, stabilizing TGF-beta receptor complex and prolonging TGF-beta receptor signaling. Deubiqutination of SMAD7 by UCHL5 has not been examined in this context (Wicks et al. 2005). Ubiquitin peptidase USP15 also deubiquitinates and stabilizes TGFBR1, leading to enhanced signaling by TGF-beta receptor complex. USP15 does not affect the ubiquitination status of SMAD7. Amplification of USP15 has recently been reported in glioblastoma, breast and ovarian cancer. In advanced glioblastoma, TGF-beta receptor signaling acts as an oncogenic factor, and USP15-mediated upregulation of TGF-beta receptor signaling may be a key factor in glioblastoma pathogenesis (Eichhorn et al. 2012). The role of UCHL5 was inferred from experiments using recombinant mouse Uchl5 and Smad7 with recombinant human TGF-beta receptors. The role of USP15 was established by experiments using human proteins.

Literature References
PubMed ID Title Journal Year
16027725 The deubiquitinating enzyme UCH37 interacts with Smads and regulates TGF-beta signalling

Wicks, SJ, Haros, K, Maillard, M, Song, L, Cohen, RE, Dijke, PT, Chantry, A

Oncogene 2005
22344298 USP15 stabilizes TGF-? receptor I and promotes oncogenesis through the activation of TGF-? signaling in glioblastoma

Eichhorn, PJ, Rodón, L, Gonzàlez-Juncà, A, Dirac, A, Gili, M, Martínez-Sáez, E, Aura, C, Barba, I, Peg, V, Prat, A, Cuartas, I, Jimenez, J, García-Dorado, D, Sahuquillo, J, Bernards, R, Baselga, J, Seoane, J

Nat Med 2012
Participants
Input
Output
Participant Of
hasEvent
Catalyst Activity
Catalyst Activity
Title
thiol-dependent ubiquitin-specific protease activity of TGFB1:TGFBR2:Ub-p-TGFBR1:Ub-SMAD7:UCHL5/USP15 [plasma membrane]
Physical Entity
TGFB1:TGFBR2:Ub-p-TGFBR1:Ub-SMAD7:UCHL5/USP15 [plasma membrane]
Activity
thiol-dependent ubiquitin-specific protease activity (0004843)
Inferred From
Uchl5 deubiquitinates TGFBR1 (Homo sapiens)
Authored
Orlic-Milacic, M  (2012-04-04)
Reviewed
Huang, T  (2012-05-14)
Created
Orlic-Milacic, M  (2012-04-03)