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Host Proteins Ku and HMGA1 As Participants of HIV-1 Transcription.

Shadrina OA, Knyazhanskaya ES, Korolev SP, Gottikh MB - Acta Naturae (2016 Jan-Mar)

Bottom Line: The latency maintenance is also a problematic question.We also describe the differential influence of the HMGA1 protein on the induced and basal transcription of HIV-1.Finally, we offer possible mechanisms for Ku and HMGA1 proteins in the proviral transcription regulation.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskie Gory, Moscow, 119991, Russia.

ABSTRACT
Human immunodeficiency virus type 1 is known to use the transcriptional machinery of the host cell for viral gene transcription, and the only viral protein that partakes in this process is Tat, the viral trans-activator of transcription. During acute infection, the binding of Tat to the hairpin at the beginning of the transcribed viral RNA recruits the PTEFb complex, which in turn hyperphosphorylates RNA-polymerase II and stimulates transcription elongation. Along with acute infection, HIV-1 can also lead to latent infection that is characterized by a low level of viral transcription. During the maintenance and reversal of latency, there are no detectable amounts of Tat protein in the cell and the mechanism of transcription activation in the absence of Tat protein remains unclear. The latency maintenance is also a problematic question. It seems evident that cellular proteins with a yet unknown nature or role regulate both transcriptional repression in the latent phase and its activation during transition into the lytic phase. The present review discusses the role of cellular proteins Ku and HMGA1 in the initiation of transcription elongation of the HIV-1 provirus. The review presents data regarding Ku-mediated HIV-1 transcription and its dependence on the promoter structure and the shape of viral DNA. We also describe the differential influence of the HMGA1 protein on the induced and basal transcription of HIV-1. Finally, we offer possible mechanisms for Ku and HMGA1 proteins in the proviral transcription regulation.

No MeSH data available.


Related in: MedlinePlus

The model of cooperative transcription regulation by HMGA1 and CTIP2. TheCTIP2-repressed 7SK/P-TEFb complex is recruited to the promoter through 7SK L2bound HMGA1 via its interaction with DNA, or with a transcription factorresiding in the promoter region [5].
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Figure 11: The model of cooperative transcription regulation by HMGA1 and CTIP2. TheCTIP2-repressed 7SK/P-TEFb complex is recruited to the promoter through 7SK L2bound HMGA1 via its interaction with DNA, or with a transcription factorresiding in the promoter region [5].

Mentions: A different model of the repressive effect of HMGA1 on transcription from theHIV-1 promoter has also been proposed [5]. Factors associated with chromatin reorganization play acrucial role in the regulation of HIV-1 transcription; the CTIP2 protein isamong these factors. The presence of CTIP2 at the promoter repressestranscription of the integrated HIV-1 genome and is typical for the latentstate of the virus. CTIP2 recruits histone deacetylases and histonemethyltransferases, thus being involved in chromatin condensation [73]. In addition, CTIP2 interacts with the Sp1and COUP-TF factors by repressing the initial stages of HIV-1 transcription[74] and is involved in delocalizationof Tat and its binding to heterochromatin-associated protein HP1 [75]. CTIP2 has recently been shown to interactwith 7SK snRNP by binding to loop L2 and the HEXIM1 protein. Within thiscomplex, CTIP2 participates 7SK-L2 HIV-1TAR Fig. 9Structures of the 7SK L2and TAR RNA regions interacting with HMGA1. The HMGA1 binding site in both RNAsis shown in green. The TAR region responsible for the interaction with Tat andCycT1 is shown in gray [4]. in therepression of Cdk9 kinase that is a component of P-TEFb [76].It has been discovered that HMGA1 can bind to CTIP2[5]. Moreover, transcription of a numberof cellular genes is negatively regulated by both proteins; some of these genesare transcribed via the P-TEFb/7SK-dependent mechanism [5].A model of joint transcriptional regulation of these genesby the HMGA1 and CTIP2 proteins has been proposed. It is assumed that HMGA1 canrecruit either CTIP2 or the CTIP2/P-TEFb/7SK snRNP complex to the promoters ofregulated genes(Fig. 11)[5].


Host Proteins Ku and HMGA1 As Participants of HIV-1 Transcription.

Shadrina OA, Knyazhanskaya ES, Korolev SP, Gottikh MB - Acta Naturae (2016 Jan-Mar)

The model of cooperative transcription regulation by HMGA1 and CTIP2. TheCTIP2-repressed 7SK/P-TEFb complex is recruited to the promoter through 7SK L2bound HMGA1 via its interaction with DNA, or with a transcription factorresiding in the promoter region [5].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837570&req=5

Figure 11: The model of cooperative transcription regulation by HMGA1 and CTIP2. TheCTIP2-repressed 7SK/P-TEFb complex is recruited to the promoter through 7SK L2bound HMGA1 via its interaction with DNA, or with a transcription factorresiding in the promoter region [5].
Mentions: A different model of the repressive effect of HMGA1 on transcription from theHIV-1 promoter has also been proposed [5]. Factors associated with chromatin reorganization play acrucial role in the regulation of HIV-1 transcription; the CTIP2 protein isamong these factors. The presence of CTIP2 at the promoter repressestranscription of the integrated HIV-1 genome and is typical for the latentstate of the virus. CTIP2 recruits histone deacetylases and histonemethyltransferases, thus being involved in chromatin condensation [73]. In addition, CTIP2 interacts with the Sp1and COUP-TF factors by repressing the initial stages of HIV-1 transcription[74] and is involved in delocalizationof Tat and its binding to heterochromatin-associated protein HP1 [75]. CTIP2 has recently been shown to interactwith 7SK snRNP by binding to loop L2 and the HEXIM1 protein. Within thiscomplex, CTIP2 participates 7SK-L2 HIV-1TAR Fig. 9Structures of the 7SK L2and TAR RNA regions interacting with HMGA1. The HMGA1 binding site in both RNAsis shown in green. The TAR region responsible for the interaction with Tat andCycT1 is shown in gray [4]. in therepression of Cdk9 kinase that is a component of P-TEFb [76].It has been discovered that HMGA1 can bind to CTIP2[5]. Moreover, transcription of a numberof cellular genes is negatively regulated by both proteins; some of these genesare transcribed via the P-TEFb/7SK-dependent mechanism [5].A model of joint transcriptional regulation of these genesby the HMGA1 and CTIP2 proteins has been proposed. It is assumed that HMGA1 canrecruit either CTIP2 or the CTIP2/P-TEFb/7SK snRNP complex to the promoters ofregulated genes(Fig. 11)[5].

Bottom Line: The latency maintenance is also a problematic question.We also describe the differential influence of the HMGA1 protein on the induced and basal transcription of HIV-1.Finally, we offer possible mechanisms for Ku and HMGA1 proteins in the proviral transcription regulation.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskie Gory, Moscow, 119991, Russia.

ABSTRACT
Human immunodeficiency virus type 1 is known to use the transcriptional machinery of the host cell for viral gene transcription, and the only viral protein that partakes in this process is Tat, the viral trans-activator of transcription. During acute infection, the binding of Tat to the hairpin at the beginning of the transcribed viral RNA recruits the PTEFb complex, which in turn hyperphosphorylates RNA-polymerase II and stimulates transcription elongation. Along with acute infection, HIV-1 can also lead to latent infection that is characterized by a low level of viral transcription. During the maintenance and reversal of latency, there are no detectable amounts of Tat protein in the cell and the mechanism of transcription activation in the absence of Tat protein remains unclear. The latency maintenance is also a problematic question. It seems evident that cellular proteins with a yet unknown nature or role regulate both transcriptional repression in the latent phase and its activation during transition into the lytic phase. The present review discusses the role of cellular proteins Ku and HMGA1 in the initiation of transcription elongation of the HIV-1 provirus. The review presents data regarding Ku-mediated HIV-1 transcription and its dependence on the promoter structure and the shape of viral DNA. We also describe the differential influence of the HMGA1 protein on the induced and basal transcription of HIV-1. Finally, we offer possible mechanisms for Ku and HMGA1 proteins in the proviral transcription regulation.

No MeSH data available.


Related in: MedlinePlus