title: The histone gene transcription factor HiNF-P stabilizes its cell cycle regulatory co-activator p220NPAT.
abstract: 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.
authors.affiliation: Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Medina
authors.forename: Andre J
authors.initials: AJ
authors.lastname: van Wijnen
authors.forename: Gary S
authors.initials: GS
authors.lastname: Stein
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stein
mesh_terms: 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
chemical_list: 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