Peer Reviewed

1

Document Type

Article

Publication Date

5-2-2012

Keywords

Apoptosis/genetics, Aurora Kinase A, Aurora Kinases, Cell Line, Tumor, Enzyme Stability, Gene Expression, Gene Expression Profiling, Humans, Neuroblastoma/*genetics/mortality, Oncogene Proteins/*genetics/metabolism, Phosphorylation, Protein Binding, Protein-Serine-Threonine Kinases/*genetics/metabolism, Receptor-Like Protein Tyrosine Phosphatases, Class 2/*genetics/metabolism, Tumor Suppressor Proteins/*genetics/metabolism, Tyrosine/metabolism

Comments

This article is available from http://www.molecular-cancer.com/

Abstract

BACKGROUND: Protein tyrosine phosphatase receptor delta (PTPRD) is a member of a large family of protein tyrosine phosphatases which negatively regulate tyrosine phosphorylation. Neuroblastoma is a major childhood cancer arising from precursor cells of the sympathetic nervous system which is known to acquire deletions and alterations in the expression patterns of PTPRD, indicating a potential tumor suppressor function for this gene. The molecular mechanism, however, by which PTPRD renders a tumor suppressor effect in neuroblastoma is unknown.

RESULTS: As a molecular mechanism, we demonstrate that PTPRD interacts with aurora kinase A (AURKA), an oncogenic protein that is over-expressed in multiple forms of cancer, including neuroblastoma. Ectopic up-regulation of PTPRD in neuroblastoma dephosphorylates tyrosine residues in AURKA resulting in a destabilization of this protein culminating in interfering with one of AURKA's primary functions in neuroblastoma, the stabilization of MYCN protein, the gene of which is amplified in approximately 25 to 30% of high risk neuroblastoma.

CONCLUSIONS: PTPRD has a tumor suppressor function in neuroblastoma through AURKA dephosphorylation and destabilization and a downstream destabilization of MYCN protein, representing a novel mechanism for the function of PTPRD in neuroblastoma.

Disciplines

Life Sciences

Citation

Meehan M, Parthasarathi L, Moran N, Jefferies CA, Foley N, Lazzari E, Murphy D, Ryan J, Ortiz B, M Fabius AW, Chan TA, Stallings RL. Protein tyrosine phosphatase receptor delta acts as a neuroblastoma tumor suppressor by destabilizing the aurora kinase a oncogene. Mol Cancer. 2012; 11:6.

PubMed ID

22305495

DOI Link

10.1186/1476-4598-11-6

Included in

Life Sciences Commons

Share

COinS