SPOP targets the immune transcription factor IRF1 for proteasomal degradation.
human
immunology
inflammation
interferon regulatory factor 1
mouse
proteasome
protein degradation
ubiquitin
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
25 08 2023
25 08 2023
Historique:
received:
05
06
2023
accepted:
16
08
2023
medline:
11
9
2023
pubmed:
25
8
2023
entrez:
25
8
2023
Statut:
epublish
Résumé
Adaptation of the functional proteome is essential to counter pathogens during infection, yet precisely timed degradation of these response proteins after pathogen clearance is likewise key to preventing autoimmunity. Interferon regulatory factor 1 (IRF1) plays an essential role as a transcription factor in driving the expression of immune response genes during infection. The striking difference in functional output with other IRFs is that IRF1 also drives the expression of various cell cycle inhibiting factors, making it an important tumor suppressor. Thus, it is critical to regulate the abundance of IRF1 to achieve a 'Goldilocks' zone in which there is sufficient IRF1 to prevent tumorigenesis, yet not too much which could drive excessive immune activation. Using genetic screening, we identified the E3 ligase receptor speckle type BTB/POZ protein (SPOP) to mediate IRF1 proteasomal turnover in human and mouse cells. We identified S/T-rich degrons in IRF1 required for its SPOP MATH domain-dependent turnover. In the absence of SPOP, elevated IRF1 protein levels functionally increased IRF1-dependent cellular responses, underpinning the biological significance of SPOP in curtailing IRF1 protein abundance.
Identifiants
pubmed: 37622993
doi: 10.7554/eLife.89951
pii: 89951
pmc: PMC10491434
doi:
pii:
Substances chimiques
Interferon Regulatory Factor-1
0
SPOP protein, human
0
Immunologic Factors
0
IRF1 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023, Schwartz, Vunjak, Budroni et al.
Déclaration de conflit d'intérêts
IS, MV, VB, AC, MM, AS, MH, Md, KH, JW, KF, JJ, TD, GV No competing interests declared, JZ JZ is a founder, shareholder and scientific advisor of Quantro Therapeutics GmbH. The Zuber lab receives research support and funding from Boehringer Ingelheim
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