KBTBD7:CUL3:RBX1 ubiquitinates NF1

Stable Identifier
R-HSA-5658424
Type
Reaction
Species
Homo sapiens
Compartment
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NF1 levels are controlled by proteasomal degradation in response to stimulation by some growth factors (Cichowski et al, 2003). Ubiquitination is mediated by the CUL3:RBX1 RING E3 ligase complex in conjunction with the BTB adaptor protein KBTBD7 (Hollstein et al, 2013). After its initial rapid degradation, NF1 protein levels are re-established shortly after growth factor treatment, allowing appropriate termination of RAS MAPK signaling (Cichowski et al, 2003). Aberrant destabilization of NF1 by CUL3:KBTBD7-mediated proteasomal degradation has been identified in cases of glioblastoma and depends on activation of PKC alpha (Cichowski et al, 2003; McGillicuddy et al, 2009; Hollstein et al, 2013).

Literature References
PubMed ID Title Journal Year
23661552 Identifying the Ubiquitin Ligase complex that regulates the NF1 tumor suppressor and Ras

Hollstein, PE, Cichowski, K

Cancer Discov 2013
12600938 Dynamic regulation of the Ras pathway via proteolysis of the NF1 tumor suppressor

Cichowski, K, Santiago, S, Jardim, M, Johnson, BW, Jacks, T

Genes Dev. 2003
19573811 Proteasomal and genetic inactivation of the NF1 tumor suppressor in gliomagenesis

McGillicuddy, LT, Fromm, JA, Hollstein, PE, Kubek, S, Beroukhim, R, De Raedt, T, Johnson, BW, Williams, SM, Nghiemphu, P, Liau, LM, Cloughesy, TF, Mischel, PS, Parret, A, Seiler, J, Moldenhauer, G, Scheffzek, K, Stemmer-Rachamimov, AO, Sawyers, CL, Brennan, C, Messiaen, L, Mellinghoff, IK, Cichowski, K

Cancer Cell 2009
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
ubiquitin protein ligase activity of KBTBD7:CUL3:RBX1 [cytosol]
Physical Entity
Activity
Orthologous Events
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Created