Your browser doesn't support javascript.
loading
Phosphorylation of the selective autophagy receptor TAX1BP1 by TBK1 and IKBKE/IKKi promotes ATG8-family protein-dependent clearance of MAVS aggregates.
White, Jesse; Choi, Young Bong; Zhang, Jiawen; Vo, Mai Tram; He, Chaoxia; Shaikh, Kashif; Harhaj, Edward W.
Afiliación
  • White J; Department of Microbiology and Immunology, Penn State College of Medicine, Hershey, PA, USA.
  • Choi YB; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Zhang J; Department of Microbiology and Immunology, Penn State College of Medicine, Hershey, PA, USA.
  • Vo MT; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • He C; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Shaikh K; Department of Microbiology and Immunology, Penn State College of Medicine, Hershey, PA, USA.
  • Harhaj EW; Department of Microbiology and Immunology, Penn State College of Medicine, Hershey, PA, USA.
Autophagy ; : 1-18, 2024 Sep 10.
Article en En | MEDLINE | ID: mdl-39193925
ABSTRACT
TAX1BP1 is a selective macroautophagy/autophagy receptor that inhibits NFKB and RIGI-like receptor (RLR) signaling to prevent excessive inflammation and maintain homeostasis. Selective autophagy receptors such as SQSTM1/p62 and OPTN are phosphorylated by the kinase TBK1 to stimulate their selective autophagy function. However, it is unknown if TAX1BP1 is regulated by TBK1 or other kinases under basal conditions or during RNA virus infection. Here, we found that TBK1 and IKBKE/IKKi function redundantly to phosphorylate TAX1BP1 and regulate its autophagic turnover through canonical macroautophagy. TAX1BP1 phosphorylation promotes its localization to lysosomes, resulting in its degradation. Additionally, we found that during vesicular stomatitis virus infection, TAX1BP1 is targeted to lysosomes in an ATG8-family protein-independent manner. Furthermore, TAX1BP1 plays a critical role in the clearance of MAVS aggregates, and phosphorylation of TAX1BP1 controls its MAVS aggrephagy function. Together, our data support a model whereby TBK1 and IKBKE license TAX1BP1-selective autophagy function to inhibit MAVS and RLR signaling.Abbreviations ATG autophagy related; BafA1 bafilomycin A1; CALCOCO2 calcium binding and coiled-coil domain 2; GFP green fluorescent protein; IFA indirect immunofluorescence assay; IFN interferon; IκB inhibitor of nuclear factor kappa B; IKK IκB kinase; IRF interferon regulatory factor; KO knockout; LAMP1 lysosomal associated membrane protein 1; LIR LC3-interacting region; MAP1LC3/LC3 microtubule associated protein 1 light chain 3; MAVS mitochondrial antiviral signaling protein; MEF mouse embryonic fibroblast; MOI multiplicity of infection; IKBKG/NEMO inhibitor of nuclear factor kappa B kinase regulatory subunit gamma; NFKB nuclear factor kappa B; OPTN optineurin; Poly(IC) polyinosinic-polycytidylic acid; RB1CC1/FIP200 RB1 inducible coiled-coil 1; RIGI RNA sensor RIG-I; RLR RIGI-like receptor; SDD-AGE semi-denaturing detergent-agarose gel electrophoresis; SeV Sendai virus; SLR SQSTM1-like receptor; SQSTM1 sequestosome 1; TAX1BP1 Tax1 binding protein 1; TBK1 TANK binding kinase 1; TNF tumor necrosis factor; TRAF TNF receptor associated factor; VSV vesicular stomatitis virus; ZnF zinc finger.
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Autophagy Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Autophagy Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos