Biochemistry and biology of the inducible multifunctional transcription factor TFII-I: 10years later

Roy, Ananda L.

doi:10.1016/j.gene.2011.10.030

Cited by 78 publications

(124 citation statements)

References 91 publications

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“…Twelve SUMO2 conjugation sites on TFII-I also were observed following heat shock (39), with six of these sites overlapping with those identified in the current analysis (see Table S3). TFII-I plays a role in numerous signaling pathways that regulate cellular gene expression, including transforming growth factor ␤, calcium, and stress signaling (55). TFII-I interacts with PIASx (Miz1/Siz2), an E3 SUMO ligase, and histone deacetylase 3 (HDAC3), as part of a transcriptional activating complex (56,57).…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Ubiquitin-Like Posttranslational Modifications Induced by the Adenovirus E4-ORF3 Protein

Sohn

Bridges

Hearing

2015

J Virol

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Viruses interact with and regulate many host metabolic pathways in order to advance the viral life cycle and counteract intrinsic and extrinsic antiviral responses. The human adenovirus (Ad) early protein E4-ORF3 forms a unique scaffold throughout the nuclei of infected cells and inhibits multiple antiviral defenses, including a DNA damage response (DDR) and an interferon response. We previously reported that the Ad5 E4-ORF3 protein induces sumoylation of Mre11 and Nbs1, which are essential for the DDR, and their relocalization into E4-ORF3-induced nuclear inclusions is required for this modification to occur. In this study, we sought to analyze a global change in ubiquitin-like (Ubl) modifications, with particular focus on SUMO3, by the Ad5 E4-ORF3 protein and to identify new substrates with these modifications. By a comparative proteome-wide approach utilizing immunoprecipitation/mass spectrometry, we found that Ubl modifications of 166 statistically significant lysine sites in 51 proteins are affected by E4-ORF3, and the proteome of modifications spans a diverse range of cellular functions. Ubl modifications of 92% of these identified sites were increased by E4-ORF3. We further analyzed SUMO3 conjugation of several identified proteins. Our findings demonstrated a role for the Ad5 E4-ORF3 protein as a regulator of Ubl modifications and revealed new SUMO3 substrates induced by E4-ORF3. (1, 2). Therefore, Ad has evolved several mechanisms to inhibit the cellular DDR early after infection. The incoming viral genome is coated with a basic viral core protein that may block recognition of the viral DNA by the cellular DDR machinery at the earliest stages of infection (3). Once Ad early protein synthesis ensues, two distinct mechanisms are employed to inhibit the DDR (1, 2). The Ad5 E1B-55K and E4-ORF6 proteins form an E3 ubiquitin (Ub) ligase complex with cellular proteins cullin 5 (CUL5), Rbx1, and elongins B and C (4, 5). Together, this complex leads to ubiquitin-mediated, proteasome-dependent degradation of cellular sensors of DNA damage, including Mre11, Rad50, and Nbs1 (the MRN complex) (6). Inhibition of cellular sensors of DNA damage blocks downstream signaling events and inhibits both DNA damage repair and cell cycle checkpoint signaling. The Ad5 E4-ORF3 protein sequesters MRN proteins into nuclear inclusions, termed nuclear tracks (7), within infected cell nuclei to inhibit MRN activity (6, 8). E4-ORF3 recruits numerous nuclear proteins into these structures, including promyelocytic leukemia (PML) and other PML-nuclear body (PML-NB)-associ- IMPORTANCE The adenovirus E4-ORF3 protein induces dynamic structural changes in the nuclei of infected cells and counteracts host antiviral responses. One of the mechanisms that accounts for this process is the relocalization and sequestration of cellular proteins into an E4-ORF3 nuclear scaffold, but little is known about how this

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Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Ubiquitin-Like Posttranslational Modifications Induced by the Adenovirus E4-ORF3 Protein

Sohn

Bridges

Hearing

2015

J Virol

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“…Specific binding partners of PKGIb are the transcription factor TFII-I and the inositol triphosphate (IP 3 ) receptor-associated PKG substrate (IRAG) (Casteel et al, 2002;Schlossmann et al, 2000). TFII-I is a multifunctional transcription factor involved in the regulation of a number of genes including c-fos (Casteel et al, 2002;Kim et al, 1998;Roy, 2012), and IRAG is essential for PKGIb-mediated intracellular calcium regulation (Schlossmann et al, 2000). The interaction with IRAG can prevent PKGIb nuclear localization and gene transactivation (Casteel et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

cGMP-dependent Protein Kinase Iβ Regulates Breast Cancer Cell Migration and Invasion via a Novel Interaction with the Actin/Myosin-associated Protein Caldesmon

Schwappacher

Rangaswami

Su-Yuo

et al. 2013

Journal of Cell Science

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SummaryThe two isoforms of type I cGMP-dependent protein kinase (PKGIa and PKGIb) differ in their first ,100 amino acids, giving each isoform unique dimerization and autoinhibitory domains. The dimerization domains form coiled-coil structures and serve as platforms for isoform-specific protein-protein interactions. Using the PKGIb dimerization domain as an affinity probe in a proteomic screen, we identified the actin/myosin-associated protein caldesmon (CaD) as a PKGIb-specific binding protein. PKGIb phosphorylated human CaD on serine 12 in vitro and in intact cells. Phosphorylation on serine 12 or mutation of serine 12 to glutamic acid (S12E) reduced the interaction between CaD and myosin IIA. Because CaD inhibits myosin ATPase activity and regulates cell motility, we examined the effects of PKGIb and CaD on cell migration and invasion. Inhibition of the NO/cGMP/PKG pathway reduced migration and invasion of human breast cancer cells, whereas PKG activation enhanced their motility and invasion. siRNA-mediated knockdown of endogenous CaD had pro-migratory and pro-invasive effects in human breast cancer cells. Reconstituting cells with wild-type CaD slowed migration and invasion; however, CaD containing a phospho-mimetic S12E mutation failed to reverse the pro-migratory and pro-invasive activity of CaD depletion. Our data suggest that PKGIb enhances breast cancer cell motility and invasive capacity, at least in part, by phosphorylating CaD. These findings identify a pro-migratory and pro-invasive function for PKGIb in human breast cancer cells, suggesting that PKGIb is a potential target for breast cancer treatment.

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“…Antibody detection of total TFII-I protein in the mouse brain suggests that most TFII-I exists in the cytoplasm (Danoff et al, 2004) where it is presumably tethered by p190RhoGAP (Jiang et al, 2005), Bruton's tyrosine kinase (Sacristán et al, 2004) or by interactions with PLC-c (Caraveo et al, 2006). We suggest that GTF2IRD2 sequestration would only be active against TFII-I or GTF2IRD1 proteins that enter the nucleus, which, in the case of the TFII-I isoforms, is largely dependent on the status of cell signaling (Roy, 2012). Therefore the relative stoichiometry of GTF2IRD2 and TFII-I isoforms in the nucleus is unstable and would be difficult to determine.…”

Section: Subcellular Localization Of Gtf2ird2 Gtf2ird1 and Tfii-imentioning

confidence: 87%

GTF2IRD2from the Williams-Beuren critical region encodes a mobile element-derived fusion protein that antagonizes the action of its related family members

Palmer

Taylor

Santucci

et al. 2012

Journal of Cell Science

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Summary GTF2IRD2 belongs to a family of transcriptional regulators (including TFII-I and GTF2IRD1) that are responsible for many of the key features of Williams-Beuren syndrome (WBS). Sequence evidence suggests that GTF2IRD2 arose in eutherian mammals by duplication and divergence from the gene encoding TFII-I. However, in GTF2IRD2, most of the C-terminal domain has been lost and replaced by the domesticated remnant of an in-frame hAT-transposon mobile element. In this first experimental analysis of function, we show that transgenic expression of each of the three family members in skeletal muscle causes significant fiber type shifts, but the GTF2IRD2 protein causes an extreme shift in the opposite direction to the two other family members. Mating of GTF2IRD1 and GTF2IRD2 mice restores the fiber type balance, indicating an antagonistic relationship between these two paralogs. In cells, GTF2IRD2 localizes to cytoplasmic microtubules and discrete speckles in the nuclear periphery. We show that it can interact directly with TFII-Ib and GTF2IRD1, and upon co-transfection changes the normal distribution of these two proteins into a punctate nuclear pattern typical of GTF2IRD2. These data suggest that GTF2IRD2 has evolved as a regulator of GTF2IRD1 and TFII-I; inhibiting their function by direct interaction and sequestration into inactive nuclear zones.

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Biochemistry and biology of the inducible multifunctional transcription factor TFII-I: 10years later

Cited by 78 publications

References 91 publications

Proteomic Analysis of Ubiquitin-Like Posttranslational Modifications Induced by the Adenovirus E4-ORF3 Protein

Proteomic Analysis of Ubiquitin-Like Posttranslational Modifications Induced by the Adenovirus E4-ORF3 Protein

cGMP-dependent Protein Kinase Iβ Regulates Breast Cancer Cell Migration and Invasion via a Novel Interaction with the Actin/Myosin-associated Protein Caldesmon

GTF2IRD2from the Williams-Beuren critical region encodes a mobile element-derived fusion protein that antagonizes the action of its related family members

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