Proteomics

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Quantitative phosphoproteomics analysis uncovers the regulatory networks of minichromosome maintenance protein 2 in lung cancer cells


ABSTRACT: Minichromosome maintenance protein 2 (MCM2) is a licensing factor for DNA replication. It interacts with other MCM proteins to comprise MCM2-7 complex, which acts as a helicase for DNA unwinding and limits DNA replication to one round per cell cycle. MCM2 has been widely used as a biomarker for proliferation in many types of cancer. However, the molecular regulation underlying MCM2 in lung cancer cells is poorly understood. In this study, we investigated the role of MCM2 in lung adenocarcinoma A549 (wild-type p53) and H1299 (null p53) cells. MCM2 overexpression increased cell proliferation in A549 cells while silencing MCM2 decreased cell proliferation in H1299 cells. We performed global quantitative phosphoproteomic analysis to uncover the important downstream networks regulated by MCM2 in lung cancer cells. We identified 1484 phosphorylation sites in 593 phosphoproteins of MCM2-overexpressed A549 cells. Of these phosphosites, 110 phosphoproteins were significantly changed in response to MCM2 overexpression. In addition, we identified 1599 phosphorylation sites in 592 phosphoproteins of MCM2-silenced H1299 cells. Of these phosphosites, 57 phosphoproteins were significantly changed in response to MCM2 silencing. The differentially regulated phosphoproteins are involved in biological functions such as RNA splicing, cell cycle and cytoskeleton regulation. Functional study demonstrated that MCM2 overexpression promoted cell migration in A549 cells. Moreover, silencing MCM2 inhibits cell migration and induces cell cycle arrest in H1299 cells. Furthermore, we observed a common phosphorylation change at Ser-99 of high mobility group protein HMG-I/HMG-Y (HMGA1) in both MCM2 overexpression and silencing, indicating an important regulatory effect of Ser-99 HMGA1 on lung cancer cells. The phosphoproteomic profiling of MCM2 in lung cancer cells provides new insight about phosphorylation networks regulated by MCM2 and reveals novel targets for lung cancer therapy.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Siao Chong  

LAB HEAD: Hsueh-Fen Juan, Ph.D.

PROVIDER: PXD002736 | Pride | 2018-10-24

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
140515-MCM2-01.raw Raw
140515-MCM2-02.raw Raw
140607-mcm2-01.raw Raw
140607-mcm2-02.raw Raw
141027-Si2-01.raw Raw
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Publications

MCM2-regulated functional networks in lung cancer by multi-dimensional proteomic approach.

Cheung Chantal Hoi Yin CHY   Hsu Chia-Lang CL   Chen Kai-Pu KP   Chong Siao-Ting ST   Wu Chang-Hsun CH   Huang Hsuan-Cheng HC   Juan Hsueh-Fen HF  

Scientific reports 20171016 1


DNA replication control is vital for maintaining genome stability and the cell cycle, perhaps most notably during cell division. Malignancies often exhibit defective minichromosome maintenance protein 2 (MCM2), a cancer proliferation biomarker that serves as a licensing factor in the initiation of DNA replication. MCM2 is also known to be one of the ATPase active sites that facilitates conformational changes and drives DNA unwinding at the origin of DNA replication. However, the biological netwo  ...[more]

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