The KRAS oncogene product is considered a major target in anticancer drug discovery 1, 2,
3. However, direct interference with KRAS signalling has not yet led to clinically useful drugs
3, 4, 5, 6, 7, 8. Correct localization and signalling by farnesylated KRAS is regulated by the …

Reversible S-palmitoylation of cysteine residues critically controls transient membrane
tethering of peripheral membrane proteins. Little is known about how the palmitoylation
machinery governs their defined localization and function. We monitored the spatially …

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 …

KRas is a major proto-oncogene product whose signaling activity depends on its level of
enrichment on the plasma membrane (PM). This PM localization relies on posttranslational
prenylation for membrane affinity, while PM specificity has been attributed to electrostatic …

A matter of common sense: A common recognition motif consisting of a negatively charged
group five to six bonds away (red) from the (thio) ester functionality (green) and a positively
charged tail group ten to twelve bonds away (blue) was identified in two native acyl protein …

The localization and signaling of S-palmitoylated peripheral membrane proteins is sustained
by an acylation cycle in which acyl protein thioesterases (APTs) depalmitoylate mislocalized
palmitoylated proteins on endomembranes. However, the APTs are themselves reversibly S …

Growth factor stimulation generates transient H-Ras activity at the plasma membrane but
sustained activity at the Golgi. Two overlapping regulatory networks control
compartmentalized H-Ras activity: the guanosine diphosphate–guanosine triphosphate …

Address reprint requests to: Nachiket Vartak, Ph.D., Department of Systems Toxicology, Leibniz
Institute for Work Physiology and Human Factors (IfADo) at TU Dortmund, 44139 Dortmund,
Germany. E‐mail E-mail address:nash@ifado.de; or Jan Hengstler, MD, Department of Systems …

The nature of living systems and their apparent resilience to the second law of
thermodynamics has been the subject of extensive investigation and imaginative
speculation. The segregation and compartmentalization of proteins is one manifestation of …

In this review we develop the argument that cholestatic liver diseases, particularly primary
biliary cholangitis and primary sclerosing cholangitis (PSC), evolve over time with
anatomically an ascending course of the disease process. The first and early lesions are in …