Reactome | Palmostatin B binds RAS depalmitoylases

Palmostatin B binds RAS depalmitoylases

Stable Identifier

R-HSA-9647991

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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Palmostatin B binds to acylthioesterases and inhibits their activity, resulting in RAS proteins that are stably palmitoylated (Dekker et al, 2010; Lin and Conibear, 2015; reviewed in Lin et al, 2017). Although this inhibition might be predicted to promote sustained RAS-dependent signaling, in fact interruption of the palmitoylation-depalmitoylation cycle results in generalized redistribution of RAS proteins to all cellular membranes, impairing function (Dekker et al, 2010). Consistent with this, Inhibition of RAS acyl protein thioesterases has been shown to have some use in restricting the proliferation of NRAS-driven melanomas (Rusch et al, 2011; Hedberg et al, 2011; Xu et al, 2012; Vujic et al, 2016).

Literature References

PubMed ID	Title	Journal	Year
26771141	Acyl protein thioesterase 1 and 2 (APT-1, APT-2) inhibitors palmostatin B, ML348 and ML349 have different effects on NRAS mutant melanoma cells Vujic, I, Sanlorenzo, M, Esteve-Puig, R, Vujic, M, Kwong, A, Tsumura, A, Murphy, R, Moy, A, Posch, C, Monshi, B, Rappersberger, K, Ortiz-Urda, S	Oncotarget	2016
20418879	Small-molecule inhibition of APT1 affects Ras localization and signaling Dekker, FJ, Rocks, O, Vartak, N, Menninger, S, Hedberg, C, Balamurugan, R, Wetzel, S, Renner, S, Gerauer, M, Schölermann, B, Rusch, M, Kramer, JW, Rauh, D, Coates, GW, Brunsveld, L, Bastiaens, PI, Waldmann, H	Nat. Chem. Biol.	2010
28630138	Targeting the Ras palmitoylation/depalmitoylation cycle in cancer Lin, DTS, Davis, NG, Conibear, E	Biochem. Soc. Trans.	2017
21905185	Development of highly potent inhibitors of the Ras-targeting human acyl protein thioesterases based on substrate similarity design Hedberg, C, Dekker, FJ, Rusch, M, Renner, S, Wetzel, S, Vartak, N, Gerding-Reimers, C, Bon, RS, Bastiaens, PI, Waldmann, H	Angew. Chem. Int. Ed. Engl.	2011
21905186	Identification of acyl protein thioesterases 1 and 2 as the cellular targets of the Ras-signaling modulators palmostatin B and M Rusch, M, Zimmermann, TJ, Bürger, M, Dekker, FJ, Görmer, K, Triola, G, Brockmeyer, A, Janning, P, Böttcher, T, Sieber, SA, Vetter, IR, Hedberg, C, Waldmann, H	Angew. Chem. Int. Ed. Engl.	2011
22144181	Inhibiting the palmitoylation/depalmitoylation cycle selectively reduces the growth of hematopoietic cells expressing oncogenic Nras Xu, J, Hedberg, C, Dekker, FJ, Li, Q, Haigis, KM, Hwang, E, Waldmann, H, Shannon, K	Blood	2012
26701913	ABHD17 proteins are novel protein depalmitoylases that regulate N-Ras palmitate turnover and subcellular localization Lin, DT, Conibear, E	Elife	2015