Glioblastoma-Specific Protein Interaction Network Identifies PP1A and CSK21 as Connecting Molecules between Cell Cycle-Associated Genes

Ladha, Jayashree and Donakonda, Sainitin and Agrawa, Shipra and Thota, Balaram and Srividya, Mallavarapu R and Sridevi, Sambandam and Arivazhagan, Arimappamagan and Thennarasu, Kandavel and Balasubramaniam, Anandh and Chandramouli, Bangalore A and Hegde, Alanga Sattiyaranjandas and Kondaiah, Paturu and Somasundaram, Kumaravel and Santosh, Vani and Rao, Satyanarayana MR (2010) Glioblastoma-Specific Protein Interaction Network Identifies PP1A and CSK21 as Connecting Molecules between Cell Cycle-Associated Genes. In: Cancer Research, 70 (16). pp. 6437-6447.

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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. Cancer Res; 70(16); 6437-47. (C)2010 AACR.

Item Type:	Journal Article
Publication:	Cancer Research
Publisher:	American Association for Cancer Research
Additional Information:	Copyright of this article belongs to American Association for Cancer Research.
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	08 Sep 2010 11:23
Last Modified:	19 Sep 2010 06:16
URI:	http://eprints.iisc.ac.in/id/eprint/32091

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