The histone gene transcription factor HiNF-P stabilizes its cell cycle regulatory co-activator p220NPAT.
Orderly progression through the cell cycle requires the transcriptional activation of histone genes to support packaging of newly replicated DNA. Induction of human histone gene expression is mediated by a co-activation complex containing transcription factor HiNF-P and its cofactor p220NPAT. Here, using cells synchronized in S-phase and in mitosis, as well as serum-stimulated cells, we have investigated how HiNF-P is regulated during the cell cycle and examined its stability relative to p220NPAT. We find that while HiNF-P is maintained at steady-state levels throughout the cell cycle, both HiNF-P and p220NPAT are actively degraded by the proteasome pathway. Importantly, elevation of HiNF-P levels enhances the stability of its co-activator p220NPAT. The HiNF-P-dependent stabilization of p220NPAT may reinforce signaling through the cyclin E/CDK2/p220NPAT pathway and contribute to coordinate control of histone gene expression.
Medina
Ricardo
R
Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
van Wijnen
Andre J
AJ
Stein
Gary S
GS
Stein
Janet L
JL
D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000378:metabolism* / Q000502:physiology; D019927:Cyclin E / Q000502:physiology; D051357:Cyclin-Dependent Kinase 2 / Q000502:physiology; D006207:Half-Life; D006367:HeLa Cells; D006657:Histones / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism* / Q000502:physiology; D043743:Ubiquitin-Protein Ligase Complexes / Q000502:physiology
D018797:Cell Cycle Proteins; D019927:Cyclin E; C442219:HINFP protein, human; D006657:Histones; C101693:NPAT protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D015534:Trans-Activators; D043743:Ubiquitin-Protein Ligase Complexes; D051357:Cyclin-Dependent Kinase 2; D046988:Proteasome Endopeptidase Complex