Cells, Год журнала: 2025, Номер 14(4), С. 304 - 304
Опубликована: Фев. 18, 2025
The IκB kinase (IKK) complex plays a central role in many signaling pathways that activate NF-κB, which turns on battery of genes important for immune response, inflammation, and cancer development. Ubiquitination is one the most prevalent post-translational modifications proteins best known targeting substrates proteasomal degradation. investigations NF-κB pathway primed unveiling non-degradative roles protein ubiquitination. NF-κB-essential modulator (NEMO) IKK regulatory subunit essential activation by diverse intrinsic extrinsic stimuli. studies centered NEMO as polyubiquitin-binding have remarkably advanced understandings how transmits signals to laid foundation determining molecular events demonstrating ubiquitination major driving element activation. Furthermore, these largely solved enigma can be activated employ distinct sets intermediaries transmitting signals. NEMO-related include optineurin, ABIN1, ABIN2, ABIN3, CEP55, ubiquitin chain receptors, play key sensing embodied different topologies polyubiquitin chains variety cellular processes body responses. Studies multifaceted promoted understanding about functions intracellular signaling, trafficking, proteostasis, DNA damage cell cycle control. In this review, I will also discuss dysfunction family protein-mediated associated with various diseases, including disorders, neurodegenerative cancer, microbial virulence factors target induce pathogenesis or manipulate host response. A profound bases valuable developing tailored approaches therapeutic purposes.
Язык: Английский