KLHL23 Activators

KLHL23 is a substrate-specific adapter protein that forms part of the E3 ubiquitin ligase complex known as Cullin-RING Ligase 3 (CRL3), also referred to as the Kelch-like ECH-associated protein 1 (KEAP1) adaptor substrate complex. The function of KLHL23 within this complex is to recognize specific protein substrates and facilitate their ubiquitination, leading to their subsequent degradation by the proteasome. KLHL23 contains multiple domains, including a BTB (bric-a-brac, tramtrack, broad complex) domain, a BACK (BTB and C-terminal Kelch) domain, and a Kelch repeat domain. These domains are involved in protein-protein interactions and substrate recognition. The Kelch repeat domain of KLHL23 interacts with target proteins, while the BTB domain mediates its association with the Cullin 3 (CUL3) scaffold protein within the CRL3 complex. Through its interaction with CUL3, KLHL23 facilitates the transfer of ubiquitin molecules onto substrate proteins, marking them for degradation by the proteasome.

The activation of KLHL23 likely involves a series of steps that regulate its assembly into the functional CRL3 ubiquitin ligase complex and its interaction with specific substrate proteins. Firstly, the expression and stability of KLHL23 may be regulated at the transcriptional and post-translational levels by various cellular signaling pathways or stimuli. These mechanisms could influence the abundance of KLHL23 and its availability for complex formation. Additionally, the recruitment of KLHL23 to the CRL3 complex and its interaction with CUL3 may be regulated by post-translational modifications or by the binding of regulatory proteins. Furthermore, the recognition of specific substrate proteins by KLHL23 may be mediated by their post-translational modifications, such as phosphorylation or acetylation, which could modulate their affinity for binding to the Kelch repeat domain of KLHL23. Overall, the activation of KLHL23 and its subsequent function within the CRL3 ubiquitin ligase complex play essential roles in regulating the turnover of specific protein substrates and maintaining cellular homeostasis.