title: Glioblastoma-specific protein interaction network identifies PP1A and CSK21 as connecting molecules between cell cycle-associated genes.
abstract: Glioblastoma (GBM; grade IV astrocytoma) is a very aggressive form of brain cancer with a poor survival and few qualified predictive markers. This study integrates experimentally validated genes that showed specific upregulation in GBM along with their protein-protein interaction information. A system level analysis was used to construct GBM-specific network. Computation of topological parameters of networks showed scale-free pattern and hierarchical organization. From the large network involving 1,447 proteins, we synthesized subnetworks and annotated them with highly enriched biological processes. A careful dissection of the functional modules, important nodes, and their connections identified two novel intermediary molecules CSK21 and protein phosphatase 1 alpha (PP1A) connecting the two subnetworks CDC2-PTEN-TOP2A-CAV1-P53 and CDC2-CAV1-RB-P53-PTEN, respectively. Real-time quantitative reverse transcription-PCR analysis revealed CSK21 to be moderately upregulated and PP1A to be overexpressed by 20-fold in GBM tumor samples. Immunohistochemical staining revealed nuclear expression of PP1A only in GBM samples. Thus, CSK21 and PP1A, whose functions are intimately associated with cell cycle regulation, might play key role in gliomagenesis.
authors.affiliation: Chromatin Biology Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Institute of Bioinformatics and Applied Biotechnology, Bangalore, India.
authors.forename: Jayashree
authors.initials: J
authors.lastname: Ladha
authors.forename: Sainitin
authors.initials: S
authors.lastname: Donakonda
authors.forename: Shipra
authors.initials: S
authors.lastname: Agrawal
authors.forename: Balaram
authors.initials: B
authors.lastname: Thota
authors.forename: Mallavarapu R
authors.initials: MR
authors.lastname: Srividya
authors.forename: Sambandam
authors.initials: S
authors.lastname: Sridevi
authors.forename: Arimappamagan
authors.initials: A
authors.lastname: Arivazhagan
authors.forename: Kandavel
authors.initials: K
authors.lastname: Thennarasu
authors.forename: Anandh
authors.initials: A
authors.lastname: Balasubramaniam
authors.forename: Bangalore A
authors.initials: BA
authors.lastname: Chandramouli
authors.forename: Alangar Sattiyaranjandas
authors.initials: AS
authors.lastname: Hegde
authors.forename: Paturu
authors.initials: P
authors.lastname: Kondaiah
authors.forename: Kumaravel
authors.initials: K
authors.lastname: Somasundaram
authors.forename: Vani
authors.initials: V
authors.lastname: Santosh
authors.forename: Satyanarayana M R
authors.initials: SM
authors.lastname: Rao
mesh_terms: D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D047390:Casein Kinase II / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D018816:Genes, cdc; D005909:Glioblastoma / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D025941:Protein Interaction Mapping; D054645:Protein Phosphatase 1 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D047390:Casein Kinase II; D054645:Protein Phosphatase 1