Reactome | KBTBD7:CUL3:RBX1 ubiquitinates NF1

KBTBD7:CUL3:RBX1 ubiquitinates NF1

Stable Identifier

R-HSA-5658424

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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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