The C-terminal tail of CSNAP attenuates the CSN complex

Maria G. Füzesi-Levi, Gili Ben-Nissan, Dina Listov, Yael Fridmann Sirkis, Zvi Hayouka, Sarel Fleishman, Michal Sharon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Protein degradation is one of the essential mechanisms that enables reshaping of the proteome landscape in response to various stimuli. The largest E3 ubiquitin ligase family that targets proteins to degradation by catalyzing ubiquitination is the cullin–RING ligases (CRLs). Many of the proteins that are regulated by CRLs are central to tumorigenesis and tumor progression, and dysregulation of the CRL family is frequently associated with cancer. The CRL family comprises ~300 complexes, all of which are regulated by the COP9 signalosome complex (CSN). Therefore, CSN is considered an attractive target for therapeutic intervention. Research efforts for targeted CSN inhibition have been directed towards inhibition of the complex enzymatic subunit, CSN5. Here, we have taken a fresh approach focusing on CSNAP, the smallest CSN subunit. Our results show that the C-terminal region of CSNAP is tightly packed within the CSN complex, in a groove formed by CSN3 and CSN8. We show that a 16 amino acid C-terminal peptide, derived from this CSN-interacting region, can displace the endogenous CSNAP subunit from the complex. This, in turn, leads to a CSNAP null phenotype that attenuates CSN activity and consequently CRLs function. Overall, our findings emphasize the potential of a CSNAP-based peptide for CSN inhibition as a new therapeutic avenue.

Original languageAmerican English
Article numbere202201634
JournalLife Science Alliance
Volume6
Issue number10
DOIs
StatePublished - Oct 2023

Bibliographical note

Publisher Copyright:
© 2023 Füzesi-Levi et al.

Fingerprint

Dive into the research topics of 'The C-terminal tail of CSNAP attenuates the CSN complex'. Together they form a unique fingerprint.

Cite this