ITRAQ-based quantitative proteomic analysis reveals that VPS35 promotes the expression of MCM2-7 genes in HeLa cells

被引:4
作者
Hong, Xian [1 ]
Wang, Tao [1 ]
Du, Juan [1 ]
Hong, Yu [1 ]
Yang, Cai-Ping [1 ]
Xiao, Wei [1 ]
Li, Yang [1 ]
Wang, Ming [1 ]
Sun, He [2 ]
Deng, Zhi-Hui [1 ]
机构
[1] Qiqihar Med Univ, Inst Med & Pharm, Lab Prot Struct & Funct, Qiqihar 161006, Heilongjiang, Peoples R China
[2] Qiqihar Med Univ, Basic Med Sch, Dept Histol & Embryol, Qiqihar 161006, Heilongjiang, Peoples R China
基金
中国国家自然科学基金;
关键词
MINICHROMOSOME MAINTENANCE PROTEINS; TO-GOLGI RETRIEVAL; WASH COMPLEX; ALPHA-SYNUCLEIN; RETROMER; FAM21; OVEREXPRESSION; PROLIFERATION; DEGRADATION; RECRUITMENT;
D O I
10.1038/s41598-022-13934-3
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Vacuolar protein sorting 35 (VPS35) is a major component of the retromer complex that regulates endosomal trafficking in eukaryotic cells. Recent studies have shown that VPS35 promotes tumor cell proliferation and affects the nuclear accumulation of its interacting partner. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-based mass spectrometry were used to measure the changes in nuclear protein abundance in VPS35-depleted HeLa cells. A total of 47 differentially expressed proteins were identified, including 27 downregulated and 20 upregulated proteins. Gene ontology (GO) analysis showed that the downregulated proteins included several minichromosome maintenance (MCM) proteins described as cell proliferation markers, and these proteins were present in the MCM2-7 complex, which is essential for DNA replication. Moreover, we validated that loss of VPS35 reduced the mRNA and protein expression of MCM2-7 genes. Notably, re-expression of VPS35 in VPS35 knockout HeLa cells rescued the expression of these genes. Functionally, we showed that VPS35 contributes to cell proliferation and maintenance of genomic stability of HeLa cells. Therefore, these findings reveal that VPS35 is involved in the regulation of MCM2-7 gene expression and establish a link between VPS35 and cell proliferation.
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页数:13
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