Dekker_2010_Nat.Chem.Biol_6_449

Reference

Title : Small-molecule inhibition of APT1 affects Ras localization and signaling - Dekker_2010_Nat.Chem.Biol_6_449
Author(s) : Dekker FJ , Rocks O , Vartak N , Menninger S , Hedberg C , Balamurugan R , Wetzel S , Renner S , Gerauer M , Scholermann B , Rusch M , Kramer JW , Rauh D , Coates GW , Brunsveld L , Bastiaens PI , Waldmann H
Ref : Nat Chemical Biology , 6 :449 , 2010
Abstract :

Cycles of depalmitoylation and repalmitoylation critically control the steady-state localization and function of various peripheral membrane proteins, such as Ras proto-oncogene products. Interference with acylation using small molecules is a strategy to modulate cellular localization--and thereby unregulated signaling--caused by palmitoylated Ras proteins. We present the knowledge-based development and characterization of a potent inhibitor of acyl protein thioesterase 1 (APT1), a bona fide depalmitoylating enzyme that is, so far, poorly characterized in cells. The inhibitor, palmostatin B, perturbs the cellular acylation cycle at the level of depalmitoylation and thereby causes a loss of the precise steady-state localization of palmitoylated Ras. As a consequence, palmostatin B induces partial phenotypic reversion in oncogenic HRasG12V-transformed fibroblasts. We identify APT1 as one of the thioesterases in the acylation cycle and show that this protein is a cellular target of the inhibitor.

PubMedSearch : Dekker_2010_Nat.Chem.Biol_6_449
PubMedID: 20418879
Gene_locus related to this paper: human-LYPLA1

Related information

Inhibitor Palmostatin-B
Gene_locus Palmostatin-B    human-LYPLA1

Citations formats

Dekker FJ, Rocks O, Vartak N, Menninger S, Hedberg C, Balamurugan R, Wetzel S, Renner S, Gerauer M, Scholermann B, Rusch M, Kramer JW, Rauh D, Coates GW, Brunsveld L, Bastiaens PI, Waldmann H (2010)
Small-molecule inhibition of APT1 affects Ras localization and signaling
Nat Chemical Biology 6 :449

Dekker FJ, Rocks O, Vartak N, Menninger S, Hedberg C, Balamurugan R, Wetzel S, Renner S, Gerauer M, Scholermann B, Rusch M, Kramer JW, Rauh D, Coates GW, Brunsveld L, Bastiaens PI, Waldmann H (2010)
Nat Chemical Biology 6 :449