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@ARTICLE{Pantoom:163508,
author = {Pantoom, Supansa and Pomorski, Adam and Huth, Katharina and
Hund, Christina and Petters, Janine and Krężel, Artur and
Hermann, Andreas and Lukas, Jan},
title = {{D}irect {I}nteraction of {ATP}7{B} and {LC}3{B} {P}roteins
{S}uggests a {C}ooperative {R}ole of {C}opper
{T}ransportation and {A}utophagy.},
journal = {Cells},
volume = {10},
number = {11},
issn = {2073-4409},
address = {Basel},
publisher = {MDPI},
reportid = {DZNE-2022-00268},
pages = {3118},
year = {2021},
note = {(CC BY)},
abstract = {Macroautophagy/autophagy plays an important role in
cellular copper clearance. The means by which the copper
metabolism and autophagy pathways interact mechanistically
is vastly unexplored. Dysfunctional ATP7B, a
copper-transporting ATPase, is involved in the development
of monogenic Wilson disease, a disorder characterized by
disturbed copper transport. Using in silico prediction, we
found that ATP7B contains a number of potential binding
sites for LC3, a central protein in the autophagy pathway,
the so-called LC3 interaction regions (LIRs). The conserved
LIR3, located at the C-terminal end of ATP7B, was found to
directly interact with LC3B in vitro. Replacing the two
conserved hydrophobic residues W1452 and L1455 of LIR3
significantly reduced interaction. Furthermore, autophagy
was induced in normal human hepatocellular carcinoma cells
(HepG2) leading to enhanced colocalization of ATP7B and LC3B
on the autophagosome membranes. By contrast, HepG2 cells
deficient of ATP7B (HepG2 ATP7B-/-) showed autophagy
deficiency at elevated copper condition. This phenotype was
complemented by heterologous ATP7B expression. These
findings suggest a cooperative role of ATP7B and LC3B in
autophagy-mediated copper clearance.},
keywords = {Amino Acid Sequence / Biological Transport: drug effects /
Copper: metabolism / Copper: pharmacology /
Copper-Transporting ATPases: chemistry / Copper-Transporting
ATPases: metabolism / Hep G2 Cells / Humans /
Microtubule-Associated Proteins: metabolism / Protein
Binding: drug effects / Protein Transport: drug effects /
ATPase copper transporting beta (Other) / HepG2 (Other) /
LC3 interaction region (Other) / Wilson disease (Other) /
autophagosome-lysosome fusion (Other) / MAP1LC3B protein,
human (NLM Chemicals) / Microtubule-Associated Proteins (NLM
Chemicals) / Copper (NLM Chemicals) / ATP7B protein, human
(NLM Chemicals) / Copper-Transporting ATPases (NLM
Chemicals)},
cin = {AG Teipel},
ddc = {570},
cid = {I:(DE-2719)1510100},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34831341},
pmc = {pmc:PMC8625360},
doi = {10.3390/cells10113118},
url = {https://pub.dzne.de/record/163508},
}