RETMEN2A and RETMEN2B oncoproteins are targets of PP1 inhibitor

Tumori. 2003 Sep-Oct;89(5):550-2. doi: 10.1177/030089160308900520.

Abstract

Medullary thyroid carcinoma (MTC) responds very poorly to chemotherapy. Mutations in the RET gene are critical for MTC pathogenesis. RET therefore represents a rational target for the development of novel MTC therapies. The accumulation of evidence from laboratory studies strongly suggests that PP1 inhibitor is a cytostatic agent for cells expressing RET oncoproteins. PP1 functions as a potent and selective inhibitor of RET oncoprotein phosphorylation, promoting its proteasomal degradation.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Medullary / drug therapy*
  • Carcinoma, Medullary / metabolism
  • Humans
  • Multiple Endocrine Neoplasia Type 2a / metabolism*
  • Multiple Endocrine Neoplasia Type 2b / metabolism*
  • Oncogene Proteins / drug effects*
  • Oncogene Proteins / metabolism*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-ret
  • Pyrazoles / pharmacology*
  • Pyrimidines / pharmacology*
  • Receptor Protein-Tyrosine Kinases / drug effects*
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / metabolism

Substances

  • 4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine
  • Antineoplastic Agents
  • Oncogene Proteins
  • Pyrazoles
  • Pyrimidines
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • Receptor Protein-Tyrosine Kinases