The promyelocytic leukemia gene product (PML) forms stable complexes with the retinoblastoma protein

Mol Cell Biol. 1998 Feb;18(2):1084-93. doi: 10.1128/mcb.18.2.1084.

Abstract

PML is a nuclear protein with growth-suppressive properties originally identified in the context of the PML-retinoic acid receptor alpha (RAR alpha) fusion protein of acute promyelocytic leukemia. PML localizes within distinct nuclear structures, called nuclear bodies, which are disrupted by the expression of PML-RAR alpha. We report that PML colocalizes with the nonphosphorylated fraction of the retinoblastoma protein (pRB) within nuclear bodies and that pRB is delocalized by PML-RAR alpha expression. Both PML and PML-RAR alpha form complexes with the nonphosphorylated form of pRB in vivo, and they interact with the pocket region of pRB. The regions of PML and PML-RAR alpha involved in pRB binding differ; in fact, the B boxes and the C-terminal region of PML, the latter of which is not present in PML-RAR alpha, are essential for the formation of stable complexes with pRB. Functionally, PML abolishes activation of glucocorticoid receptor-regulated transcription by pRB, whereas PML-RAR alpha further increases it. Our results suggest that PML may be part of transcription-regulatory complexes and that the oncogenic potential of the PML-RAR alpha protein may derive from the alteration of PML-regulated transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Division
  • Humans
  • Inclusion Bodies / metabolism
  • Macromolecular Substances
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Nuclear Proteins*
  • Oncogene Proteins, Fusion / metabolism*
  • Promoter Regions, Genetic
  • Promyelocytic Leukemia Protein
  • Protein Binding
  • Receptors, Glucocorticoid / metabolism
  • Retinoblastoma Protein / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins

Substances

  • Macromolecular Substances
  • Neoplasm Proteins
  • Nuclear Proteins
  • Oncogene Proteins, Fusion
  • Promyelocytic Leukemia Protein
  • Receptors, Glucocorticoid
  • Retinoblastoma Protein
  • Transcription Factors
  • Tumor Suppressor Proteins
  • promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
  • PML protein, human