Aryl Hydrocarbon Receptor Defect Attenuates Mitogen-Activated Signaling through Leucine-Rich Repeats and Immunoglobulin-like Domains 1 (LRIG1)-Dependent EGFR Degradation

Autor: Po Lin Liao, Ching Hao Li, Chen Chen Lee, Hong Kai Chen, Yu Cheng Lee, Yen Ju Chan, Chi Hao Tsai, Han Lin Hsu
Jazyk: angličtina
Rok vydání: 2021
Předmět:
leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1)
Pulmonary Disease
Chronic Obstructive
Epidermal growth factor
Biology (General)
Receptor
chronic obstructive pulmonary disease (COPD)
Lung
Spectroscopy
Mice
Knockout
Membrane Glycoproteins
biology
Chemistry
Cell Cycle
General Medicine
respiratory system
epidermal growth factor receptor (EGFR)
Computer Science Applications
Cell biology
Ubiquitin ligase
Up-Regulation
ErbB Receptors
Mitogen-activated protein kinase
Signal transduction
Signal Transduction
QH301-705.5
Leucine-rich repeat
ADAM17 Protein
Catalysis
Article
Inorganic Chemistry
Animals
Humans
Physical and Theoretical Chemistry
Molecular Biology
QD1-999
aryl hydrocarbon receptor (AHR)
Epidermal Growth Factor
Organic Chemistry
Cell Cycle Checkpoints
Aryl hydrocarbon receptor
Clone Cells
respiratory tract diseases
Mice
Inbred C57BL
cell proliferation
Proteasome
Receptors
Aryl Hydrocarbon
A549 Cells
Proteolysis
biology.protein
a disintegrin and metalloprotease 17 (ADAM17)
Mitogens
Zdroj: International Journal of Molecular Sciences, Vol 22, Iss 9988, p 9988 (2021)
International Journal of Molecular Sciences
Volume 22
Issue 18
ISSN: 1661-6596
1422-0067
Popis: Aryl hydrocarbon receptor (AHR) genomic pathway has been well-characterized in a number of respiratory diseases. In addition, the cytoplasmic AHR protein may act as an adaptor of E3 ubiquitin ligase. In this study, the physiological functions of AHR that regulate cell proliferation were explored using the CRISPR/Cas9 system. The doubling-time of the AHR-KO clones of A549 and BEAS-2B was observed to be prolonged. The attenuation of proliferation potential was strongly associated with either the induction of p27Kip1 or the impairment in mitogenic signal transduction driven by the epidermal growth factor (EGF) and EGF receptor (EGFR). We found that the leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1), a repressor of EGFR, was induced in the absence of AHR in vitro and in vivo. The LRIG1 tends to degrade via a proteasome dependent manner by interacting with AHR in wild-type cells. Either LRIG1 or a disintegrin and metalloprotease 17 (ADAM17) were accumulated in AHR-defective cells, consequently accelerating the degradation of EGFR, and attenuating the response to mitogenic stimulation. We also affirmed low AHR but high LRIG1 levels in lung tissues of chronic obstructive pulmonary disease (COPD) patients. This might partially elucidate the sluggish tissue repairment and developing inflammation in COPD patients.
Databáze: OpenAIRE
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