Retinoic acid induces the degradation of the leukemogenic protein encoded by the promyelocytic leukemia gene fused to the retinoic acid receptor alpha gene

Nutr Rev. 2000 Jul;58(7):211-4. doi: 10.1111/j.1753-4887.2000.tb01865.x.

Abstract

Acute promyelocytic leukemia (APL) cells carry a mutated gene that is the result of a translocation in which the retinoic acid receptor alpha (RAR alpha) gene is fused to the promyelocytic leukemia (PML) gene, coding for a fusion protein, PML/RAR alpha. Its presence is the single event that causes APL in transgenic mice. All-trans-retinoic acid (atRA) induces the proteolytic degradation of PML/RAR alpha by ubiquitination and proteolysis. RAR alpha itself is also degraded by atRA treatment, a process representing a possible feedback mechanism to turn off RAR alpha's stimulation of transcription.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Artificial Gene Fusion
  • Humans
  • Leukemia, Promyelocytic, Acute / drug therapy
  • Leukemia, Promyelocytic, Acute / genetics
  • Neoplasm Proteins / genetics*
  • Nuclear Proteins*
  • Promyelocytic Leukemia Protein
  • Receptors, Retinoic Acid / genetics*
  • Transcription Factors / genetics*
  • Translocation, Genetic / genetics
  • Tretinoin / pharmacology
  • Tretinoin / physiology*
  • Tumor Suppressor Proteins
  • Vitamin A / therapeutic use

Substances

  • Antineoplastic Agents
  • Neoplasm Proteins
  • Nuclear Proteins
  • Promyelocytic Leukemia Protein
  • Receptors, Retinoic Acid
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Vitamin A
  • PML protein, human
  • Tretinoin