Association of JC Virus Large T Antigen with Myelin Basic Protein Transcription Factor (MEF-1/Purα) in Hypomyelinated Brains of Mice Transgenically Expressing T Antigen

Tretiakova, Anna P.; Otte, Jessica; Croul, Sidney; Kim, Julie H.; Johnson, Edward M.; Amini, Shohreh; Khalili, Kamel

doi:10.1128/jvi.73.7.6076-6084.1999

Cited by 14 publications

(8 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As mentioned previously, Purα has the ability to interact with several cellular and viral regulatory proteins. In particular its interaction with the human neurotropic JC virus regulatory protein, T‐antigen, was shown both in vivo in the brains of transgenic mice expressing T‐antigen (Tretiakova et al, 1999) and in vitro in a glial cell culture system (Gallia et al, 1998). As Purα regulates the promoter activity of the gene expressing T‐antigen and by associating with T‐antigen, modulates the activity of this protein, we sought to perform a reciprocal experiment to examine the effect of T‐antigen on the Purα promoter and to determine whether association of T‐antigen and Purα affects the ability of Purα to downregulate the Purα promoter in glial cells.…”

Section: Resultsmentioning

confidence: 99%

“…Development of transgenic mice with expression of JCV T‐antigen in brain and the occurrence of hypomyelination which correlated with low level expression of MBP suggested that the interaction of JCV T‐antigen with Purα may have a negative effect on transcription of the MBP promoter. Support for this notion came from studies showing the association of T‐antigen and Purα in mouse brain experiencing demyelination (Tretiakova et al, 1999).…”

mentioning

confidence: 98%

See 1 more Smart Citation

Regulation of Pur? gene transcription: Evidence for autoregulation of Pur? promoter

et al. 2001

Self Cite

View full text Add to dashboard Cite

The single-stranded DNA and RNA binding protein, Puralpha, has recently received special attention as this protein, by associating with the specific nucleotide sequence (GGN repeats) and/or several important cellular and viral proteins regulates crucial biological events such as transcription, replication, and cell proliferation. In this study, we focused on the promoter activity of the Puralpha upstream DNA sequence and demonstrated that the sequence spanning 6,000 nucleotides upstream of the Puralpha transcription start site has promoter activity in various cell types. Results from promoter deletion studies revealed that this region encompasses various regulatory motifs which differentially participate in the promoter activity of Puralpha in various cells. The transcription start site of Puralpha is surrounded by the GA/GC-rich sequence which exhibits the ability to interact with Puralpha, suggesting a role for autoregulation of Puralpha transcription. Results from co-transfection studies revealed that ectopic expression of Puralpha reduced transcriptional activity of the Puralpha promoter and the region located between amino acid residues, 1-85 of Puralpha is important for the observed autoregulatory event. The regulatory protein of the human neurotropic virus, JCV, T-antigen, which interacts with Puralpha, decreased transcriptional activity of the Puralpha promoter. Co-expression of JCV T-antigen and Puralpha had no significant effect on the suppression of Puralpha gene transcription by either protein. The importance of this finding in light of earlier results showing down regulation of Puralpha during JCV infection of glial cells is discussed.

show abstract

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 98%

Regulation of Pur? gene transcription: Evidence for autoregulation of Pur? promoter

et al. 2001

Self Cite

View full text Add to dashboard Cite

show abstract

“…In this case, Sp1 in not directly involved in basal expression of JCV genome. Moreover, Tretiakova et al (1999a) demonstrated that Sp1 associated Purα regulates myelin basic protein (MBP) expression, especially during brain development, and that TAg can bind Purα and downregulate MBP transcription (Tretiakova et al, 1999a,b). As a result in oligodendrocytes, JCV may lead to hypomyelination in two distinct ways: utilizing Sp1 for activation of JCV early genes (TAg in particular) and decreasing the level of MBP gene expression through association of T antigen with Purα.…”

Section: Discussionmentioning

confidence: 99%

Investigation on the role of cell transcriptional factor Sp1 and HIV‐1 TAT protein in PML onset or development

Mischitelli

Fioriti

Videtta

et al. 2005

Journal Cellular Physiology

View full text Add to dashboard Cite

JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML), characterized by multiple areas of demyelination and attendant loss of brain function. PML is often associated with immunodepression and it is significantly frequent in AIDS patients. The viral genome is divided into early and late genes, between which lies a non-coding control region (NCCR) that regulates JCV replication and presents a great genetic variability. The NCCR of JCV archetype (CY strain) is divided into six regions: A-F containing binding sites for cell factors involved in viral transcription. Deletions and enhancements of these binding sites characterize JCV variants, which could promote viral gene expression and could be more suitable for the onset or development of PML. Therefore, we evaluated by means of polymerase chain reaction (PCR) the presence of JCV genome in cerebrospinal fluid (CSF) of HIV positive and negative subjects both with PML and after sequencing, we analyzed the viral variants found focusing on Sp1 binding sites (box B and D) and up-TAR sequence (box C). It is known that Sp1 activates JCV early promoter and can contribute in maintaining methylation-free CpG islands in active genes, while up-TAR sequence is important for HIV-1 Tat stimulation of JCV late promoter. Our results showed that in HIV-positive subjects all NCCR structures presented enhancements of up-TAR element, whereas in HIV-negative subjects both Sp1 binding sites were always retained. Therefore, we can support the synergism HIV-1/JCV in CNS and we can hypothesize that both Sp1 binding sites could be important to complete JCV replication cycle in absence of HIV-coinfection.

show abstract

“…It is also possible that the pur proteins may associate with the BC1 RNP via protein—protein interactions with the Translin, as pur α has been reported to interact with several cellular and viral proteins to perform diverse functions (Johnson et al, 1995; Gallia et al, 1999; Tretiakova et al, 1999 a , b ). Moreover, it was also reported that combinatorial interactions between pur α, pur β, and a Y‐box protein, MSY1, may have functional significance in regulating transcriptional activity of the smooth muscle α‐actin gene (Kelm et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

The Single‐Stranded DNA‐ and RNA‐Binding Proteins Pur α and Pur β Link BC1 RNA to Microtubules Through Binding to the Dendrite‐Targeting RNA Motifs

Ohashi

Kobayashi²,

Omori³

et al. 2000

Journal of Neurochemistry

View full text Add to dashboard Cite

Neural BC1 RNA is distributed in neuronal dendrites as RNA-protein complexes (BC1 RNPs) containing Translin. In this study, we demonstrated that the single-stranded DNA-and RNA-binding protein pur ␣ and its isoform, pur ␤, which have been implicated in control of DNA replication and transcription, linked BC1 RNA to microtubules (MTs). The binding site was within the 5Ј proximal region of BC1 RNA containing putative dendrite-targeting RNA motifs rich in G and U residues, suggesting that in the cytoplasm of neurons, these nuclear factors are involved in the BC1 RNA transport along dendritic MTs. The pur proteins were not components of BC1 RNP but appeared to associate with MTs in brain cells. Therefore, it is suggested that they may transiently interact with the RNP during transport. In this respect, the interaction of pur proteins with BC1 RNA could be regulated by the Translin present within the RNP, because the binding mode of these two classes of proteins (pur proteins and Translin) to the dendrite-targeting RNA motifs was mutually exclusive. As the motifs are well conserved in microtubule-associated protein 2a/b mRNA as well, the pur proteins may also play a role(s) in the dendritic transport of a subset of mRNAs. Key Words: BC1 RNABrain-Neuronal dendrite -Pur ␣ and pur ␤ proteinsMicrotubule-binding protein-RNA transport. J. Neurochem. 75, 1781Neurochem. 75, -1790Neurochem. 75, (2000.Neural BC1 RNA is expressed selectively in rodent brain (Sutcliffe et al., 1982;Anzai et al., 1986) and is distributed in neuronal dendrites (Tiedge et al., 1991) in the form of ribonucleoprotein particles (RNPs) (Kobayashi et al., 1991;Cheng et al., 1996). In a previous study, we demonstrated the presence of two copies of y-, h-element homologous sequences in BC1 RNA [nucleotides (nt) 1-22 and 47-76] (see Fig. 1) (Muramatsu et al., 1998), and we detected two RNA-binding proteins using the radiolabeled 3Ј distal y-, h-elements (nt 47-76) as a probe, which co-purified with BC1 RNP (Kobayashi et al., 1998;Muramatsu et al., 1998). One of these proteins was mouse Translin and the other was a 37-kDa protein. In addition to these observations, we demonstrated the dendritic distribution of Translin protein in hippocampal neurons in primary culture (Kobayashi et al., 1998), suggesting that Translin is involved in the dendritic translocation of BC1 RNP. Recently, Translin was also detected in dendrites of a subset of neurons of the mouse brain (Wu et al., 1999). Wu et al. (1997) reported that testis/brain RNA-binding protein (TB-RBP), which was originally identified as a y-, h-element-binding protein (Kwon and Hecht, 1991), is the mouse homologue of Translin. They also reported that TB-RBP has translational repressor activity (Kwon and Hecht, 1993) and links a subset of mRNAs to microtubules (MTs) in vitro through binding to their y-, h-sequence elements (Han et al., 1995a). These observations in turn suggested that dendritic MTs are also involved in the process of BC1 RNP transport and that this RNP may have regulatory roles...

show abstract

Association of JC Virus Large T Antigen with Myelin Basic Protein Transcription Factor (MEF-1/Purα) in Hypomyelinated Brains of Mice Transgenically Expressing T Antigen

Cited by 14 publications

References 31 publications

Regulation of Pur? gene transcription: Evidence for autoregulation of Pur? promoter

Regulation of Pur? gene transcription: Evidence for autoregulation of Pur? promoter

Investigation on the role of cell transcriptional factor Sp1 and HIV‐1 TAT protein in PML onset or development

The Single‐Stranded DNA‐ and RNA‐Binding Proteins Pur α and Pur β Link BC1 RNA to Microtubules Through Binding to the Dendrite‐Targeting RNA Motifs

Contact Info

Product

Resources

About