Palmostatin B binds RAS depalmitoylases

Stable Identifier
Reaction [binding]
Homo sapiens
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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

Murphy, R, Posch, C, Rappersberger, K, Vujic, M, Moy, A, Esteve-Puig, R, Kwong, A, Sanlorenzo, M, Monshi, B, Tsumura, A, Ortiz-Urda, S, Vujic, I

Oncotarget 2016
20418879 Small-molecule inhibition of APT1 affects Ras localization and signaling

Waldmann, H, Bastiaens, PI, Rusch, M, Vartak, N, Brunsveld, L, Rocks, O, Coates, GW, Menninger, S, Kramer, JW, Gerauer, M, Balamurugan, R, Renner, S, Rauh, D, Schölermann, B, Dekker, FJ, Wetzel, S, Hedberg, C

Nat. Chem. Biol. 2010
28630138 Targeting the Ras palmitoylation/depalmitoylation cycle in cancer

Conibear, E, Davis, NG, Lin, DTS

Biochem. Soc. Trans. 2017
21905185 Development of highly potent inhibitors of the Ras-targeting human acyl protein thioesterases based on substrate similarity design

Renner, S, Waldmann, H, Bon, RS, Dekker, FJ, Bastiaens, PI, Gerding-Reimers, C, Wetzel, S, Vartak, N, Rusch, M, Hedberg, C

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

Triola, G, Waldmann, H, Rusch, M, Dekker, FJ, Bürger, M, Brockmeyer, A, Janning, P, Sieber, SA, Vetter, IR, Zimmermann, TJ, Hedberg, C, Görmer, K, Böttcher, T

Angew. Chem. Int. Ed. Engl. 2011
22144181 Inhibiting the palmitoylation/depalmitoylation cycle selectively reduces the growth of hematopoietic cells expressing oncogenic Nras

Shannon, K, Li, Q, Xu, J, Waldmann, H, Dekker, FJ, Hwang, E, Haigis, KM, Hedberg, C

Blood 2012
26701913 ABHD17 proteins are novel protein depalmitoylases that regulate N-Ras palmitate turnover and subcellular localization

Conibear, E, Lin, DT

Elife 2015
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