Dataset Information

Proteome and phosphoproteome analysis of monkey brains with PINK1 depletion

ABSTRACT: PINK1 protein is highly expressed in primate brains. CRISPR-Cas9-mediated depletion of PINK1in fetal and adult monkey brains causes severe neurodegeneration without affecting mitochondrial proteins and morphology.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Macaca Mulatta (rhesus Macaque)

TISSUE(S): Brain

SUBMITTER: Yunpeng Zhang

LAB HEAD: Liao Lujian

PROVIDER: PXD023520 | Pride | 2022-02-16

REPOSITORIES: Pride

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Publications

PINK1 kinase dysfunction triggers neurodegeneration in the primate brain without impacting mitochondrial homeostasis.

Yang Weili W Guo Xiangyu X Tu Zhuchi Z Chen Xiusheng X Han Rui R Liu Yanting Y Yan Sen S Wang Qi Q Wang Zhifu Z Zhao Xianxian X Zhang Yunpeng Y Xiong Xin X Yang Huiming H Yin Peng P Wan Huida H Chen Xingxing X Guo Jifeng J Yan Xiao-Xin XX Liao Lujian L Li Shihua S Li Xiao-Jiang XJ

Protein & cell 20211120 1

In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodeg ...[more]

PMID: 34800266

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Project description:Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers with high mortality rate. Smoking is one of the established risk factors of ESCC. However, there is limited data on molecular alterations associated with cigarette smoke exposure in esophageal cells. Understanding the effects of cigarette smoke on esophageal squamous epithelial cells at a molecular level would lead to a better understanding of the pathobiology of ESCC which has implications for identification of early biomarkers and therapeutic targets. To investigate the effect of cigarette smoke exposure, we developed a cell line model where Het1A cells (non-neoplastic human esophageal epithelial cells) were chronically treated with cigarette smoke condensate (CSC) for 2 months, 4 months, 6 months and 8 months. We carried out comparative proteomic, phosphoproteomic and whole exome sequencing analyses on CSC treated and untreated cells. Increased cell proliferation and invasion of Het1A cells was observed after chronic exposure to cigarette smoke. Using quantitative proteomic and phosphoproteomic analyses, we identified 56 proteins and 296 phosphoproteins that showed differential expression. Bioinformatics analysis of differentially expressed proteins and phosphoproteins showed enrichment of molecules involved in DNA damage response pathway. Whole exome sequencing (WES) of CSC treated and untreated cells also revealed mutations and copy number alterations in genes associated with DNA damage response. By correlating WES, proteomic and phosphoproteomic results, we observed potential loss of function in HMGN2 and MED1 that were reported as potential tumor suppressors and are known to play important role in DNA damage response. We also observed decreased expression of HMGN2 in tissue section of ESCC. Overexpression of HMGN2 and MED1 lead to decreased proliferative and invasive ability of CSC treated cells. These findings suggest that cigarette smoke affects genes and proteins associated with DNA damage response pathways which might play a vital role in development of ESCC.

Dataset Information

Proteome and phosphoproteome analysis of monkey brains with PINK1 depletion

Publications

PINK1 kinase dysfunction triggers neurodegeneration in the primate brain without impacting mitochondrial homeostasis.

Similar Datasets

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