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Updated: Jun 3, 2026

Cigarette Smoke Exposure in Mice using a Whole-Body Inhalation System
Published on: October 22, 2020
Cigarette smoke suppresses the ubiquitin-dependent degradation of OLC1
Xiaojing Zhang1, Ting Xiao, Shujun Cheng
1State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
Abstract:
The newly identified gene, overexpressed in lung cancer 1 (OLC1), is highly expressed as OLC1 protein in the tumor tissues of lung cancer patients with histories of cigarette smoking. However, the underlying mechanisms of how the gene is affected by cigarette smoke have been poorly characterized. In this study, we investigated how OLC1 is regulated in lung cancer cells by cigarette smoke condensate (CSC). Compared to the controls, CSC treatment increased OLC1 protein levels in a dose- and time-dependent manner without affecting OLC1 mRNA levels in lung cancer cells. Ubiquitination of OLC1 protein was blocked upon CSC treatment. Biochemical analysis revealed that the ubiquitin E3 ligase anaphase promoting complex (APC) and its activators cell-division cycle protein 20 (CDC20) and cadherin-1 (CDH1) are responsible for the degradation of OLC1. However, upon introducing CSC the binding of OLC1 to the proteins CDC20, CDH1, and APC2 was impaired. These results demonstrate that CSC regulates OLC1 expression in lung cancer cells by compromising its ubiquitination and subsequent degradation through the ubiquitin E3 ligase APC.
Insights
Cigarette smoke condensate increases OLC1 protein in lung cancer by blocking its ubiquitination and degradation via the anaphase promoting complex (APC). This study reveals a novel mechanism linking smoking to OLC1 regulation in lung cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The gene overexpressed in lung cancer 1 (OLC1) is highly expressed in lung tumors of smokers.
- Mechanisms linking cigarette smoke to OLC1 regulation are poorly understood.
Purpose of the Study:
- Investigate how cigarette smoke condensate (CSC) regulates OLC1 in lung cancer cells.
- Elucidate the molecular pathways involved in CSC-mediated OLC1 modulation.
Main Methods:
- Treatment of lung cancer cells with CSC.
- Analysis of OLC1 mRNA and protein levels.
- Assessment of OLC1 ubiquitination.
- Co-immunoprecipitation assays to study protein interactions.
Main Results:
- CSC increased OLC1 protein levels in a dose- and time-dependent manner, without affecting OLC1 mRNA.
- CSC treatment inhibited OLC1 ubiquitination.
- CSC impaired the binding of OLC1 to CDC20, CDH1, and APC2, key components of the ubiquitin-proteasome system.
Conclusions:
- CSC regulates OLC1 protein levels in lung cancer cells by inhibiting its ubiquitination and subsequent degradation.
- This regulation occurs through interference with the anaphase promoting complex (APC) ubiquitin ligase pathway.
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