Palmitoylation: policing protein stability and traffic

TL;DR: In this paper , a palmitoylation-dependent translocation mechanism for Protocadherin 7 (PCDH7) was uncovered, which contributes to the reorganization of the cortical cytoskeleton during cell division.

Abstract: ABSTRACT Protein S- acylation is a lipid-based, often reversible post-translational modification that can regulate many aspects of protein behavior, including subcellular localization, protein-interactions, and activity. Emerging evidence has identified roles for individual protein acyltransferases encoded by the ZDHHC in cancers, yet the roles of de- S- acylation enzymes are less clear. Recent evidence suggests that acyl-protein thioesterase (APT1)/ LYPLA1 can impact epithelial-mesenchymal transition and metastasis. This study integrates patient datasets, CRISPR dependency data, and in vitro assays to find APT1 as a context-dependent vulnerability in triple-negative breast cancer (TNBC). Despite the highest protein abundance in luminal MCF7 cells, basal-like MDA-MB-468 cells exhibited the most prominent specific APT1 activity, reflecting subtype-specific regulation. Inhibition of APT1 with ML348 increased S -acylation of nuclear and mitochondrial proteins without altering global acylation. Functionally, APT1 inhibition reduced cell proliferation while inducing minimal apoptosis, consistent with cytostatic growth arrest. Cell-cycle analysis revealed G1 accumulation and reduced S/G2 transition, linking proteomic changes to impaired replication. These findings establish APT1 as a regulator of TNBC proliferation through dynamic de- S- acylation of cell-cycle and mitochondrial proteins, highlighting it as a potential therapeutic vulnerability in aggressive breast cancers.

TL;DR: This study combines protein palmitoylation characteristics with machine learning to identify four core genes (ASPA, RBM20, COL4A1, and MAL) for gastric cancer diagnosis, achieving an optimal AUC of 0.963 with Gradient Boosting Machine model.

TL;DR: The ubiquitin system plays important roles in the control of numerous processes, including cell-cycle progression, signal transduction, transcriptional regulation, receptor down-regulation, and endocytosis as mentioned in this paper.

TL;DR: The emphasis in this review is on the enzymology of prenyl protein processing and the functional significance ofPrenylation in cellular events.

TL;DR: The role of myristate and palmitate in promoting membrane binding as well as specific membrane targeting will be reviewed, with emphasis on the Src family of tyrosine protein kinases and alpha subunits of heterotrimeric G proteins.

TL;DR: It is shown that the specific subcellular distribution of H- and Nras guanosine triphosphate–binding proteins is generated by a constitutive de/reacylation cycle that operates on palmitoylated proteins, driving their rapid exchange between the plasma membrane (PM) and the Golgi apparatus.