p65 Negatively regulates transcription of the cyclin E gene.
NF-kappaB family members play a pivotal role in many cellular and organismal functions, including the cell cycle. As an activator of cyclin D1 and p21(Waf1) genes, NF-kappaB has been regarded as a critical modulator of cell cycle. To study the involvement of NF-kappaB in G(1)/S phase regulation, the levels of selected transcriptional regulators were monitored following overexpression of NF-kappaB or its physiological induction by tumor necrosis factor-alpha. Cyclin E gene was identified as a major transcriptional target of NF-kappaB. Recruitment of NF-kappaB to the cyclin E promoter was correlated with the transrepression of cyclin E gene. Ligation-mediated PCR and micrococcal nuclease-Southern assays suggested the nucleosomal nature of this region while chromatin immunoprecipitation analysis confirmed the exchange of cofactors following tumor necrosis factor-alpha treatment or release from serum starvation. There was a progressive reduction in cyclin E transcription along with the accumulation of catalytically inactive cyclin E-cdk2 complexes and arrest of cells in G(1)/S-phase. Thus, our study clearly establishes NF-kappaB as a negative regulator of cell cycle through transcriptional repression of cyclin E.
Janbandhu
Vaibhao C
VC
Virology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Singh
Anup K
AK
Mukherji
Atish
A
Kumar
Vijay
V
D002384:Catalysis; D002453:Cell Cycle; D002460:Cell Line; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D019927:Cyclin E / Q000096:biosynthesis*; D004247:DNA / Q000737:chemistry; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006801:Humans; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D016133:Polymerase Chain Reaction; D050863:Synaptotagmin I / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D019927:Cyclin E; D016328:NF-kappa B; D050863:Synaptotagmin I; D014409:Tumor Necrosis Factor-alpha; D004247:DNA
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