Protein tyrosine phosphatase receptor delta acts as a neuroblastoma tumor suppressor by destabilizing the aurora kinase a oncogene

Autor: Derek Murphy, Berenice Ortiz, Maria Meehan, Armida W. M. Fabius, Niamh H. Foley, Laavanya Parthasarathi, Jacqueline Ryan, Timothy A. Chan, Niamh Moran, Caroline A. Jefferies, Elisa Lazzari, Raymond L. Stallings
Rok vydání: 2012
Předmět:
Cancer Research
Gene Expression
Apoptosis
Protein tyrosine phosphatase
Protein Serine-Threonine Kinases
lcsh:RC254-282
Receptor tyrosine kinase
Neuroblastoma
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Aurora Kinases
Cell Line
Tumor
Enzyme Stability
MYCN
medicine
Humans
Phosphorylation
neoplasms
Aurora Kinase A
030304 developmental biology
Oncogene Proteins
AURKA
0303 health sciences
biology
Gene Expression Profiling
Tumor Suppressor Proteins
Research
Receptor-Like Protein Tyrosine Phosphatases
Class 2
PTPRD
Tumor suppressor
Tyrosine phosphorylation
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
Oncology
chemistry
Receptor-Like Protein Tyrosine Phosphatases
030220 oncology & carcinogenesis
ROR1
biology.protein
Cancer research
Tyrosine
Molecular Medicine
N-Myc
Protein Binding
Zdroj: Molecular Cancer, Vol 11, Iss 1, p 6 (2012)
Molecular Cancer
ISSN: 1476-4598
DOI: 10.1186/1476-4598-11-6
Popis: 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.
Databáze: OpenAIRE
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