Transcription factor Sp3 is regulated by acetylation

Braun, Harald; Koop, Ronald; Ertmer, Alexa; Nacht, Silvina; Suske, Guntram

doi:10.1093/nar/29.24.4994

Cited by 134 publications

(119 citation statements)

References 32 publications

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“…In support of this assumption, treatment of Hep3B cells and SL2 cells with HDAC inhibitor TSA caused the phosphorylation of Sp1, leading to the activation of its transcriptional activity (Choi et al, 2002). We also do not exclude the possibility that the transcriptional activation of p21 WAF1/Cip1 by apicidin might be mediated by hyperacetylation of Sp1 and/or Sp3, because Sp3 can be acetylated in vivo (Braun et al, 2001). Also, other nonhistone proteins such as the p53 or E2F transcription factor are thought to be regulated by reversible acetylation (Martinez-Balbas et al, 2000;Prives and Manley, 2001).…”

Section: Discussionmentioning

confidence: 92%

Expression of p21WAF1/Cip1 through Sp1 sites by histone deacetylase inhibitor apicidin requires PI 3-kinase–PKCε signaling pathway

et al. 2003

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We previously reported that the activation of p21 WAF1/Cip1 transcription by histone deacetylase inhibitor apicidin was mediated through Sp1 sites and pointed to the possible participation of protein kinase C (PKC). In this study, we investigated the role and identity of the specific isoforms of PKC involved and identified phosphatidylinositol 3-kinase (PI 3-kinase) as an upstream effector in HeLa cells. Using an isoform-specific pharmacological inhibitor of PKC, a PKCe dominant-negative mutant, and antisense oligonucleotide to inhibit PKCe specifically, we found that among PKC isoforms, PKCe was required for the p21 WAF1/ Cip1 expression by apicidin. In addition to PKCe, PI 3-kinase appeared to participate in the activation of p21 WAF1/Cip1 promoter by apicidin, since inactivation of PI 3-kinase either by transient expression of dominantnegative mutant of PI 3-kinase or its specific inhibitors, LY294002 and wortmannin, attenuated the activation of p21 WAF1/Cip1 promoter and p21 WAF1/Cip1 protein expression by apicidin. Furthermore, membrane translocation of PKCe in response to apicidin was blocked by the PI 3-kinase inhibitor, indicating the role of PI 3-kinase as an upstream molecule of PKCe in the p21 WAF1/Cip1 promoter activation by apicidin. However, the p21 WAF1/Cip1 expression by apicidin appeared to be independent of the histone hyperacetylation, since apicidin-induced histone hyperacetylation of p21 WAF1/Cip1 promoter region was not affected by inhibition of PI 3-kinase and PKC, suggesting that the chromatin remodeling through the histone hyperacetylation alone might not be sufficient for the expression of p21 WAF1/Cip1 by apicidin. Taken together, these results suggest that the PI 3-kinase-PKCe signaling pathway plays a pivotal role in the expression of the p21 WAF1/Cip1 by apicidin.

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Section: Discussionmentioning

confidence: 92%

Expression of p21WAF1/Cip1 through Sp1 sites by histone deacetylase inhibitor apicidin requires PI 3-kinase–PKCε signaling pathway

et al. 2003

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“…Acetylation of Sp1 likely occurs at lysine residues within the DNA-binding domain (31), whereas the location of acetylation of Sp3 has not yet been precisely determined. Previously, we have shown that mutation of the SUMO lysine 551 impaired acetylation of Sp3 in vivo (32). This finding suggested originally that the same lysine residue that is a target for SUMOylation is also a target for acetylation.…”

Section: An Upstream Open Reading Frame Is Involved In Regulating Sp3mentioning

confidence: 87%

Complexity of Translationally Controlled Transcription Factor Sp3 Isoform Expression

Sapetschnig¹,

Koch²,

Rischitor

et al. 2004

Journal of Biological Chemistry

100

105

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Sp3 is a ubiquitous transcription factor closely related to Sp1. Both proteins contain a highly conserved DNA-binding domain close to the C terminus and two glutamine-rich domains in the N-terminal moiety. Immunoblot analyses of Sp3 reveal a striking complex protein pattern of up to eight distinct species. This pattern is not observed in Sp3-deficient cell lines showing that all signals reflect Sp3 antigen. In this study, we have unraveled the complexity of Sp3 expression. We show that four isoforms of Sp3 that retain different parts of the N terminus are expressed in vivo. The four isoforms derive from alternative translational start sites at positions 1, 37, 856, and 907. An upstream open reading frame located at position ؊47 to ؊18 regulates expression of the two long isoforms. Unlike Sp1, none of the Sp3 isoforms is glycosylated. However, all four isoforms become SUMO-modified in vivo and in vitro specifically and exclusively at lysine residue 551. The transcriptional activity of the two long isoforms strongly depends on the promoter settings, whereas the small isoforms appear to be inactive. The transcriptional activity of all the Sp3 isoforms is regulated by SUMO modification. Our results demonstrate that Sp3 has many unique features and is not simply a functional equivalent of Sp1.The transcription factor Sp3 is a ubiquitously expressed member of the Sp family of transcription factor that is involved in the expression and regulation of many genes, including housekeeping genes, tissue-specifically expressed genes, viral genes, and cell cycle-regulated genes (1, 2). Sp3 contains a highly conserved DNA-binding domain close to the C terminus and two glutamine-rich activation domains in the N-terminal moiety. The expression pattern, the structure, and the DNAbinding properties of Sp3 are very similar to Sp1, which suggested originally that these two proteins exert similar functions. The physiological roles of Sp1 and Sp3, however, appear to be significantly different. Sp1 knock-out mouse embryos are severely retarded in growth, and die after day 10 of embryonic development (3). Sp3-deficient embryos develop until birth, but die invariably of respiratory failure immediately after birth (4). In addition, late tooth and bone developmental processes are impaired in Sp3Ϫ/Ϫ mice (4, 5).Functional analyses of the transcriptional properties of Sp1 and Sp3 also revealed significant differences between these two transcription factors (6). On many reporter constructs containing multiple Sp-binding sites Sp3 is, unlike Sp1, inactive or acts only as a weak activator (7). The molecular basis for the inactivity of Sp3 under these conditions has been mapped to an inhibitory domain located between the second glutamine-rich activation domain and the zinc finger region (8). More recently, it was shown that Sp3 is post-translationally modified by the small ubiquitin-like modifier (SUMO) 1 within its inhibitory domain and that SUMO modification leads to inactivation (9, 10).All previously published studies with Sp3 (more than 500 ...

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“…Proteins that can be either sumoylated or ubiquitylated include I B␣ in the NF-B transcription pathway (Desterro et al 1998), pathogenic Huntington's disease protein Huntingtin (Steffan et al 2004), and the DNA polymerase auxiliary factor, PCNA (Hoege et al 2002). Further, sumoylation-deacetylation interplay has been suggested for the transcription factor Sp3 (Braun et al 2001;Ross et al 2002).…”

Section: Discussionmentioning

confidence: 99%

Histone sumoylation is a negative regulator in Saccharomyces cerevisiae and shows dynamic interplay with positive-acting histone modifications

Nathan¹,

Ingvarsdottir²,

Sterner³

et al. 2006

Genes Dev.

306

257

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Covalent histone post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitylation play pivotal roles in regulating many cellular processes, including transcription, response to DNA damage, and epigenetic control. Although positive-acting post-translational modifications have been studied in Saccharomyces cerevisiae, histone modifications that are associated with transcriptional repression have not been shown to occur in this yeast. Here, we provide evidence that histone sumoylation negatively regulates transcription in S. cerevisiae. We show that all four core histones are sumoylated and identify specific sites of sumoylation in histones H2A, H2B, and H4. We demonstrate that histone sumoylation sites are involved directly in transcriptional repression. Further, while histone sumoylation occurs at all loci tested throughout the genome, slightly higher levels occur proximal to telomeres. We observe a dynamic interplay between histone sumoylation and either acetylation or ubiquitylation, where sumoylation serves as a potential block to these activating modifications. These results indicate that sumoylation is the first negative histone modification to be identified in S. cerevisiae and further suggest that sumoylation may serve as a general dynamic mark to oppose transcription.

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Transcription factor Sp3 is regulated by acetylation

Cited by 134 publications

References 32 publications

Expression of p21WAF1/Cip1 through Sp1 sites by histone deacetylase inhibitor apicidin requires PI 3-kinase–PKCε signaling pathway

Expression of p21WAF1/Cip1 through Sp1 sites by histone deacetylase inhibitor apicidin requires PI 3-kinase–PKCε signaling pathway

Complexity of Translationally Controlled Transcription Factor Sp3 Isoform Expression

Histone sumoylation is a negative regulator in Saccharomyces cerevisiae and shows dynamic interplay with positive-acting histone modifications

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