Phosphatase POPX2 interferes with cell cycle by interacting with Chk1

Autor: Farouq Azizan, Yen Ling Koon, Pu Rum Kim, Raphael T.C. Lee, Cheng-Gee Koh, Keng-Hwee Chiam, Dylan Hong Zheng Koh
Přispěvatelé: School of Biological Sciences, Interdisciplinary Graduate School (IGS), Bioinformatics Institute, A*STAR
Rok vydání: 2020
Předmět:
Partner of PIX 2 Phosphatase
0301 basic medicine
DNA damage
Phosphatase
Cell
Regulator
Biology
Proteomics
Models
Biological
Cell Line
Substrate Specificity
Protein–protein interaction
03 medical and health sciences
0302 clinical medicine
Protein Domains
Protein Interaction Mapping
Phosphoprotein Phosphatases
medicine
Humans
Amino Acid Sequence
Gene Silencing
CHEK1
Phosphorylation
Molecular Biology
Phylogeny
Cell Cycle
Reproducibility of Results
Biological sciences [Science]
Cell Biology
Cell cycle
Cell biology
030104 developmental biology
medicine.anatomical_structure
Structural Homology
Protein
030220 oncology & carcinogenesis
Checkpoint Kinase 1
Protein–Protein Interactions
biological phenomena
cell phenomena
and immunity
DNA Damage
Protein Binding
Research Paper
Developmental Biology
Zdroj: Cell Cycle
ISSN: 1551-4005
1538-4101
DOI: 10.1080/15384101.2020.1711577
Popis: Protein-protein interaction network analysis plays critical roles in predicting the functions of target proteins. In this study, we used a combination of SILAC-MS proteomics and bioinformatic approaches to identify Checkpoint Kinase 1 (Chk1) as a possible POPX2 phosphatase interacting protein. POPX2 is a PP2C phosphatase that has been implicated in cancer cell invasion and migration. From the Domain-Domain Interaction (DDI) database, we first determined that the PP2C phosphatase domain interacts with Pkinase domain. Subsequently, 46 proteins with Pkinase domain were identified from POPX2 SILAC-MS data. We then narrowed down the leads and confirmed the biological interaction between Chk1 and POPX2. We also found that Chk1 is a substrate of POPX2. Chk1 is a key regulator of the cell cycle and is activated when the cell suffers DNA damage. Our approach has led us to identify POPX2 as a regulator of Chk1 and can interfere with the normal function of Chk1 at G1-S transition of the cell cycle in response to DNA damage. Ministry of Education (MOE) Nanyang Technological University This work was supported by the Nanyang Technological University [SUG]; Ministry of Education (Singapore) [2016- T1-002-081].
Databáze: OpenAIRE
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