FOXK2 targeting by the SCF-E3 ligase subunit FBXO24 for ubiquitin mediated degradation modulates mitochondrial respiration.

ABSTRACT: FOXK2 is a crucial transcription factor implicated in a wide array of biological activities and yet understanding of its molecular regulation at the level of protein turnover is limited. Here, we identify that FOXK2 undergoes degradation in lung epithelia in the presence of the virulent pathogens Pseudomonas aeruginosa and Klebsiella pneumoniae through ubiquitin-proteasomal processing. FOXK2 through its carboxyl terminus (aa 428-478) binds the Skp-Cullin-F-box ubiquitin E3 ligase subunit FBXO24 that mediates multisite polyubiquitylation of the transcription factor resulting in its nuclear degradation. FOXK2 was detected within the mitochondria and targeted depletion of the transcription factor or cellular expression of FOXK2 mutants devoid of key carboxy terminal domains significantly impa

SUBMITTER: El-Mergawy R 

PROVIDER: S-EPMC11209018 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature