KBTBD7:CUL3:RBX1 ubiquitinates NF1

Stable Identifier
Reaction [transition]
Homo sapiens
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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
12600938 Dynamic regulation of the Ras pathway via proteolysis of the NF1 tumor suppressor

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

Genes Dev. 2003
23661552 Identifying the Ubiquitin Ligase complex that regulates the NF1 tumor suppressor and Ras

Cichowski, K, Hollstein, PE

Cancer Discov 2013
19573811 Proteasomal and genetic inactivation of the NF1 tumor suppressor in gliomagenesis

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

Cancer Cell 2009
Catalyst Activity

ubiquitin protein ligase activity of KBTBD7:CUL3:RBX1 [cytosol]

Orthologous Events
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