Chemical Proteomics Reveals Protein Tyrosination Extends Beyond the Alpha-Tubulins in Human Cells

Makarov, Dmytro und Kielkowski, Pavel (2022): Chemical Proteomics Reveals Protein Tyrosination Extends Beyond the Alpha-Tubulins in Human Cells. In: Chembiochem, Bd. 23, Nr. 23

Abstract

Tubulin detyrosination-tyrosination cycle regulates the stability of microtubules. With respect to alpha-tubulins, the tyrosination level is maintained by a single tubulin-tyrosine ligase (TTL). However, the precise dynamics and tubulin isoforms which undergo (de)tyrosination in neurons are unknown. Here, we exploit the substrate promiscuity of the TTL to introduce an O-propargyl-l-tyrosine to neuroblastoma cells and neurons. Mass spectrometry-based chemical proteomics in neuroblastoma cells using the O-propargyl-l-tyrosine probe revealed previously discussed tyrosination of TUBA4A, MAPRE1, and other non-tubulin proteins. This finding was further corroborated in differentiating neurons. Together we present the method for tubulin tyrosination profiling in living cells. Our results show that detyrosination-tyrosination is not restricted to alpha-tubulins with coded C-terminal tyrosine and is thus involved in fine-tuning of the tubulin and non-tubulin proteins during neuronal differentiation.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department Chemie
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 1439-4227
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 491502892
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 325871075