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

TY - JOUR

T1 - The promyelocytic leukemia gene product (PML) forms stable complexes with the retinoblastoma protein.

AU - Alcalay, M

AU - Tomassoni, L

AU - Colombo, E

AU - Stoldt, S

AU - Grignani, F

AU - Fagioli, M

AU - Szekely, L

AU - Helin, K

AU - Pelicci, P G

N1 - Keywords: Cell Division; Humans; Inclusion Bodies; Macromolecular Substances; Neoplasm Proteins; Nuclear Proteins; Oncogene Proteins, Fusion; Promoter Regions (Genetics); Protein Binding; Receptors, Glucocorticoid; Retinoblastoma Protein; Transcription Factors; Transcription, Genetic; Tumor Cells, Cultured; Tumor Suppressor Proteins

PY - 1998

Y1 - 1998

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 9448006

SN - 0270-7306

VL - 18

SP - 1084

EP - 1093

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

IS - 2

ER -