title: Cigarette smoke suppresses the ubiquitin-dependent degradation of OLC1.
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.
authors: State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
authors: Xiaojing
authors: X
authors: Zhang
authors: Ting
authors: T
authors: Xiao
authors: Shujun
authors: S
authors: Cheng
authors: Tong
authors: T
authors: Tong
authors: Yanning
authors: Y
authors: Gao
mesh_terms: D000595:Amino Acid Sequence; D064173:Anaphase-Promoting Complex-Cyclosome; D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000378:metabolism; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000378:metabolism*; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000378:metabolism*; D014026:Nicotiana / Q000633:toxicity*; D025801:Ubiquitin / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; C533705:IST1 protein, human; D015513:Oncogene Proteins; D012906:Smoke; D025801:Ubiquitin; C577488:CDC20 protein, human; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases