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.
|Titolo:||The promyelocytic leukemia gene product (PML) forms stable complexes with the retinoblastoma protein|
|Parole Chiave:||Retinoblastoma Protein; Humans; Inclusion Bodies; Receptors, Glucocorticoid; Transcription, Genetic; Protein Binding; Tumor Suppressor Proteins; Macromolecular Substances; Promoter Regions, Genetic; Neoplasm Proteins; Tumor Cells, Cultured; Nuclear Proteins; Transcription Factors; Oncogene Proteins, Fusion; Cell Division|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||feb-1998|
|Digital Object Identifier (DOI):||10.1128/MCB.18.2.1084|
|Appare nelle tipologie:||01 - Articolo su periodico|