APT1-Mediated Cross-Talk Between Palmitoylation and Phosphorylation Events of the BCR Pathway Sensitizes CLL Cells Towards BCR-Associated Kinase Inhibitors

Berg, Valeska; Baatout, Dunja; Wendtner, Clemens; Hallek, Michael; Frenzel, Lukas P.

doi:10.1182/blood.v128.22.4361.4361

Cited by 1 publication

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The combinatorial interplay of the two has an important role in protein trafficking and localization due to the reversibility of both modifications that can be rapidly and dynamically regulated ( Stram and Payne, 2016 ; Zaballa and van der Goot, 2018 ). Studies have shown varied types of interactions including synergistic, reciprocal, and precursor regulation between the two PTMs ( Salaun, Greaves, and Chamberlain, 2010 ; Shipston, 2011 ; Gauthier-Kemper et al, 2014 ; Moritz et al, 2015 ; Berg et al, 2016 ; Main and Fuller, 2022 ). The addition of the negatively charged phosphate group can modulate membrane binding by interacting with the positively charged head groups in the lipid bilayer or interrupt the interaction of polybasic domains of proteins with negatively charged head groups ( Quatela et al, 2008 ; Vitrac et al, 2017 ).…”

Section: Hitting the Mark: Interrelationship Of Palmitoylation And Ot...mentioning

confidence: 99%

“…In some cases, palmitoylation acts as a precursor for phosphorylation. For example, APT1-mediated depalmitoylation is required to precede phosphorylation within the Akt/mTOR/p70S6 signalling pathway ( Berg et al, 2016 ). Regardless of the nature of regulation, aberrant phosphorylation is a prevalent characteristic of neurodegenerative diseases, particularly in those involving protein aggregation ( Tenreiro, Eckermann, and Outeiro, 2014 ; Xia, Prokop, and Giasson, 2021 ).…”

Section: Hitting the Mark: Interrelationship Of Palmitoylation And Ot...mentioning

confidence: 99%

See 1 more Smart Citation

Lost in traffic: consequences of altered palmitoylation in neurodegeneration

et al. 2023

View full text Add to dashboard Cite

One of the first molecular events in neurodegenerative diseases, regardless of etiology, is protein mislocalization. Protein mislocalization in neurons is often linked to proteostasis deficiencies leading to the build-up of misfolded proteins and/or organelles that contributes to cellular toxicity and cell death. By understanding how proteins mislocalize in neurons, we can develop novel therapeutics that target the earliest stages of neurodegeneration. A critical mechanism regulating protein localization and proteostasis in neurons is the protein-lipid modification S-acylation, the reversible addition of fatty acids to cysteine residues. S-acylation is more commonly referred to as S-palmitoylation or simply palmitoylation, which is the addition of the 16-carbon fatty acid palmitate to proteins. Like phosphorylation, palmitoylation is highly dynamic and tightly regulated by writers (i.e., palmitoyl acyltransferases) and erasers (i.e., depalmitoylating enzymes). The hydrophobic fatty acid anchors proteins to membranes; thus, the reversibility allows proteins to be re-directed to and from membranes based on local signaling factors. This is particularly important in the nervous system, where axons (output projections) can be meters long. Any disturbance in protein trafficking can have dire consequences. Indeed, many proteins involved in neurodegenerative diseases are palmitoylated, and many more have been identified in palmitoyl-proteomic studies. It follows that palmitoyl acyl transferase enzymes have also been implicated in numerous diseases. In addition, palmitoylation can work in concert with cellular mechanisms, like autophagy, to affect cell health and protein modifications, such as acetylation, nitrosylation, and ubiquitination, to affect protein function and turnover. Limited studies have further revealed a sexually dimorphic pattern of protein palmitoylation. Therefore, palmitoylation can have wide-reaching consequences in neurodegenerative diseases.

show abstract