Small molecule inhibition of protein depalmitoylation as a new approach towards downregulation of oncogenic Ras signalling.
The H- and N-Ras GTPases are prominent examples of proteins, whose localizations and signalling capacities are regulated by reversible palmitoylations and depalmitoylations. Recently, the novel small molecule inhibitor palmostatin B has been described to inhibit Ras depalmitoylation and to revert the phenotype of oncogenic HRasG12V transformed cells. This demonstrates that palmostatin B is a tool to investigate the biochemical effects of the inhibition of cellular Ras depalmitoylation on Ras signalling, which is relevant for oncology. Furthermore, it is to be expected that many proteins, of which the signalling capacities depend on reversible palmitoylation, will be discovered in the near future. This stresses the urgent need for further development of small molecule inhibitors of palmitoylation and depalmitoylation in order to study their functions in cellular signalling.
Department of Pharmaceutical Gene Modulation, Groningen Research Institute of Pharmacy, Anthonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. f.j.dekker@rug.nl
Frank J
FJ
Dekker
Christian
C
Hedberg
D000818:Animals; D015536:Down-Regulation; D006801:Humans; D050356:Lipid Metabolism; D054878:Lipoylation; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism*
D018631:ras Proteins