The MAPK Signaling Cascade is a Central Hub in the Regulation of Cell Cycle, Apoptosis and Cytoskeleton Remodeling by Tripeptidyl-Peptidase II

Ramakrishna Sompallae; Vaia Stavropoulou; Mathieu Houde; Maria G. Masucci

doi:10.4137/GRSB.S882

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The MAPK Signaling Cascade is a Central Hub in the Regulation of Cell Cycle, Apoptosis and Cytoskeleton Remodeling by Tripeptidyl-Peptidase II

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The MAPK Signaling Cascade is a Central Hub in the Regulation of Cell Cycle, Apoptosis and Cytoskeleton Remodeling by Tripeptidyl-Peptidase II

Ramakrishna Sompallae, Vaia Stavropoulou, Mathieu Houde and Maria G. Masucci

Gene regulation and systems biology, Vol.2(2), pp.253-265

01/01/2008

DOI: 10.4137/GRSB.S882

PMCID: PMC2733081

PMID: 19787088

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Abstract

Tripeptidyl-peptidase II (TPPII) is a serine peptidase highly expressed in malignant Burkitt’s lymphoma cells (BL). We have previously shown that overexpression of TPPII correlates with chromosomal instability, centrosomal and mitotic spindle abnormalities and resistance to apoptosis induced by spindle poisons. Furthermore, TPPII knockdown by RNAi was associated with endoreplication and the accumulation of polynucleated cells that failed to complete cell division, indicating a role of TPPII in the cell cycle. Here we have applied a global approach of gene expression analysis to gain insights on the mechanism by which TPPII regulates this phenotype. mRNA profiling of control and TPPII knockdown BL cells identified one hundred and eighty five differentially expressed genes. Functional categorization of these genes highlighted major physiological functions such as apoptosis, cell cycle progression, cytoskeleton remodeling, proteolysis, and signal transduction. Pathways and protein interactome analysis revealed a significant enrichment in components of MAP kinases signaling. These findings suggest that TPPII influences a wide network of signaling pathways that are regulated by MAPKs and exerts thereby a pleiotropic effect on biological processes associated with cell survival, proliferation and genomic instability.

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Title: Subtitle: The MAPK Signaling Cascade is a Central Hub in the Regulation of Cell Cycle, Apoptosis and Cytoskeleton Remodeling by Tripeptidyl-Peptidase II
Creators: Ramakrishna Sompallae - Karolinska Institutet
Vaia Stavropoulou - Karolinska Institutet
Mathieu Houde - Karolinska Institutet
Maria G. Masucci - Karolinska Institutet
Resource Type: Journal article
Publication Details: Gene regulation and systems biology, Vol.2(2), pp.253-265
DOI: 10.4137/GRSB.S882
PMID: 19787088
PMCID: PMC2733081
NLM abbreviation: Gene Regul Syst Bio
ISSN: 1177-6250
eISSN: 1177-6250
Publisher: Libertas Academica
Language: English
Date published: 01/01/2008
Academic Unit: Pathology
Record Identifier: 9984634907002771

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