Glioblastoma-specific protein interaction network identifies PP1A and CSK21 as connecting molecules between cell cycle-associated genes.
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.
Ladha
Jayashree
J
Chromatin Biology Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Institute of Bioinformatics and Applied Biotechnology, Bangalore, India.
Donakonda
Sainitin
S
Agrawal
Shipra
S
Thota
Balaram
B
Srividya
Mallavarapu R
MR
Sridevi
Sambandam
S
Arivazhagan
Arimappamagan
A
Thennarasu
Kandavel
K
Balasubramaniam
Anandh
A
Chandramouli
Bangalore A
BA
Hegde
Alangar Sattiyaranjandas
AS
Kondaiah
Paturu
P
Somasundaram
Kumaravel
K
Santosh
Vani
V
Rao
Satyanarayana M R
SM
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
D047390:Casein Kinase II; D054645:Protein Phosphatase 1