Proteomics

Dataset Information

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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 is sensitive to degradation by the virulent pathogens P. aeruginosa and K. pneumoniae in lung epithelia 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 mitochondria and targeted depletion of the transcription factor or cellular expression of FOXK2 mutants devoid of key carboxyl-terminal domains significantly impaired mitochondrial function. In experimental bacterial pneumonia, Fbxo24 heterozygous mice exhibited preserved mitochondrial function and Foxk2 protein levels compared to wild-type littermates. The results suggest a new mode of regulatory control of mitochondrial energetics through modulation of FOXK2 cellular abundance.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung, Epithelial Cell

SUBMITTER: Rabab ElMergawy  

LAB HEAD: Rama Mallampalli

PROVIDER: PXD050221 | Pride | 2024-07-03

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
FOXK2Data.sf3 Other
FoxK2FlagFBXO24IP1.raw Raw
FoxK2FlagFBXO24IP2.raw Raw
FoxK2FlagFBXO24IP3.raw Raw
FoxK2FlagIP1.raw Raw
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Publications

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

El-Mergawy Rabab R   Chafin Lexie L   Ovando-Ricardez Jose A JA   Rosas Lorena L   Tsai MuChun M   Rojas Mauricio M   Mora Ana L AL   Mallampalli Rama K RK  

The Journal of biological chemistry 20240510 6


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  ...[more]

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