Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P62988 (
Ubiquitin
)
4,326
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Invading microbial pathogens can be eliminated selectively by xenophagy.
Ubiquitin
-mediated autophagy receptors are phosphorylated by TANK-binding kinase 1 (TBK1) and recruited to ubiquitinated bacteria to facilitate autophagosome formation during xenophagy, but the molecular mechanism underlying TBK1 activation in response to microbial infection is not clear. Here, we show that bacterial infection increases Ca
2+
levels to activate TBK1 for xenophagy via the Ca
2+
-binding protein
TBC1 domain family member 9
(
TBC1D9
). Mechanistically, the ubiquitin-binding region (UBR) and Ca
2+
-binding motif of
TBC1D9
mediate its binding with ubiquitin-positive bacteria, and
TBC1D9
knockout suppresses TBK1 activation and subsequent recruitment of the ULK1 complex. Treatment with a Ca
2+
chelator impairs
TBC1D9
-ubiquitin interactions and TBK1 activation during xenophagy.
TBC1D9
is also recruited to damaged mitochondria through its UBR and Ca
2+
-binding motif, and is required for TBK1 activation during mitophagy. These results indicate that
TBC1D9
controls TBK1 activation during xenophagy and mitophagy through Ca
2+
-dependent ubiquitin-recognition.
...
PMID:TBC1D9 regulates TBK1 activation through Ca
2+
signaling in selective autophagy. 3203 38
