Control of e2f1 and PCNA by Drosophila transcription factor DREF

Kawamori, Akihito; Shimaji, Kouhei; Yamaguchi, Masamitsu

doi:10.1002/dvg.22419

Cited by 3 publications

(2 citation statements)

References 68 publications

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“…Mutations of the two residues required for the interaction with DREF lead to inability of E1A to transform primary rodent cells in cooperation with E1B (19), although it is unclear whether this is due to the loss of binding to DREF or DYRK1A. The Drosophila homologue of DREF is an important coregulator of genes involved in control of cellular growth (47), and the human protein has also been implicated in regulation of similar cellular activities (36). Therefore, it is tempting to speculate that, in addition to regulating viral growth, interaction of E1A with DREF is important for cell cycle induction although further experimentation is needed to test this possibility.…”

Section: Discussionmentioning

confidence: 99%

Adenovirus E1A Targets the DREF Nuclear Factor To Regulate Virus Gene Expression, DNA Replication, and Growth

Radko

Koleva

James

et al. 2014

J Virol

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The adenovirus E1A gene is the first gene expressed upon viral infection. E1A remodels the cellular environment to maximize permissivity for viral replication. E1A is also the major transactivator of viral early gene expression and a coregulator of a large number of cellular genes. E1A carries out its functions predominantly by binding to cellular regulatory proteins and altering their activities. The unstructured nature of E1A enables it to bind to a large variety of cellular proteins and form new molecular complexes with novel functions. The C terminus of E1A is the least-characterized region of the protein, with few known binding partners. Here we report the identification of cellular factor DREF (ZBED1) as a novel and direct binding partner of E1A. Our studies identify a dual role for DREF in the viral life cycle. DREF contributes to activation of gene expression from all viral promoters early in infection. Unexpectedly, it also functions as a growth restriction factor for adenovirus as knockdown of DREF enhances virus growth and increases viral genome copy number late in the infection. We also identify DREF as a component of viral replication centers. E1A affects the subcellular distribution of DREF within PML bodies and enhances DREF SUMOylation. Our findings identify DREF as a novel E1A C terminus binding partner and provide evidence supporting a role for DREF in viral replication. IMPORTANCEThis work identifies the putative transcription factor DREF as a new target of the E1A oncoproteins of human adenovirus. DREF was found to primarily localize with PML nuclear bodies in uninfected cells and to relocalize into virus replication centers during infection. DREF was also found to be SUMOylated, and this was enhanced in the presence of E1A. Knockdown of DREF reduced the levels of viral transcripts detected at 20 h, but not at 40 h, postinfection, increased overall virus yield, and enhanced viral DNA replication. DREF was also found to localize to viral promoters during infection together with E1A. These results suggest that DREF contributes to activation of viral gene expression. However, like several other PML-associated proteins, DREF also appears to function as a growth restriction factor for adenovirus infection.T he interaction of the adenovirus early 1A (E1A) proteins with mammalian regulatory factors has been heavily exploited to elucidate the molecular basis by which they control cellular processes (1-5). Studying the interactions of E1A with new cellular targets provides an exciting opportunity to identify and dissect critical mechanisms controlling mammalian transcription, growth, and differentiation, as well as to identify novel viral regulatory mechanisms. The organization of E1A into short peptide motifs (MoRFs) (6) involved in protein interactions has significantly enriched our understanding of eukaryotic protein function. Identification and characterization of novel MoRFs within E1A allow their subsequent detection in other proteins, which suggests novel interactions leading to signifi...

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Section: Discussionmentioning

confidence: 99%

Adenovirus E1A Targets the DREF Nuclear Factor To Regulate Virus Gene Expression, DNA Replication, and Growth

Radko

Koleva

James

et al. 2014

J Virol

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“…Activation of E2f1 leads to upregulation of CycE 20 and genes required for DNA replication and M-phase [98,99]. Although the knowledge about exact function and interactions of E2f1 is still poor, it has been known to differ in tissue/cell type and even position of the cell within the same tissue [100].…”

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confidence: 99%

Genetic mechanisms regulating proliferation and cell specification in the Drosophila embryonic CNS

Bahrampour¹

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Cover picture/illustration: Confocal image of the Drosophila embryos fillets at stage 12, stained for Dpn (green), Pros (red), GsbN (blue) and PH3 (white). The front cover shows the control, and the back cover is the combinatorial misexpression of da-Gal/UAS-ase, -SoxN, -wor, -hb, -Kr, -nub leads to the widespread generation of NBs and GMCs, and extensive proliferation throughout the ectoderm, contrary the underlying VNC shows normal segmentation.Published articles have been reprinted with the permission of the copyright holder.Printed in Sweden by LiU-Tryck, Linköping, Sweden, 2017

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Developmental Hypothyroxinemia and Hypothyroidism Reduce Proliferation of Cerebellar Granule Neuron Precursors in Rat Offspring by Downregulation of the Sonic Hedgehog Signaling Pathway

Wang

Dong

et al. 2013

Mol Neurobiol

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Iodine deficiency (ID)-induced hypothyroxinemia and hypothyroidism during development result in dysfunction of the central nervous system, affecting psychomotor and motor function, although the underlying mechanisms causing these alterations are still unclear. Therefore, our aim is to study the effects of developmental hypothyroxinemia, caused by mild ID, and developmental hypothyroidism, caused by severe ID or methimazole (MMZ), on the proliferation of cerebellar granule neuron precursors (CGNPs), an excellent experimental model of cerebellar development and function. The sonic hedgehog (Shh) signaling pathway is essential for CGNP proliferation, and as such, its activation is also investigated here. A maternal hypothyroxinemia model was established in Wistar rats by administrating a mild ID diet, and two maternal hypothyroidism models were developed either by administrating a severe ID diet or MMZ water. Our results showed that hypothyroxinemia and hypothyroidism reduced proliferation of CGNPs on postnatal day (PN) 7, PN14, and PN21. Accordingly, the mean intensity of proliferating cell nuclear antigen and Ki67 nuclear antigen immunofluorescence was reduced in the mild ID, severe ID, and MMZ groups. Moreover, maternal hypothyroxinemia and hypothyroidism reduced expression of the Shh signaling pathway on PN7, PN14, and PN21. Our study supports the hypothesis that developmental hypothyroxinemia induced by mild ID, and hypothyroidism induced by severe ID or MMZ, reduce the proliferation of CGNPs, which may be ascribed to the downregulation of the Shh signaling pathway.

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Control of e2f1 and PCNA by Drosophila transcription factor DREF

Cited by 3 publications

References 68 publications

Adenovirus E1A Targets the DREF Nuclear Factor To Regulate Virus Gene Expression, DNA Replication, and Growth

Adenovirus E1A Targets the DREF Nuclear Factor To Regulate Virus Gene Expression, DNA Replication, and Growth

Genetic mechanisms regulating proliferation and cell specification in the Drosophila embryonic CNS

Developmental Hypothyroxinemia and Hypothyroidism Reduce Proliferation of Cerebellar Granule Neuron Precursors in Rat Offspring by Downregulation of the Sonic Hedgehog Signaling Pathway

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