The transcription of the intercellular adhesion molecule-1 is regulated by Ets transcription factors

Launoit, Yvan de; Audette, Marie; Pelczar, Hélène; Plaza, Serge; Baert, Jean-Luc

doi:10.1038/sj.onc.1201726

Cited by 60 publications

(62 citation statements)

References 24 publications

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“…Similar results were obtained in RK13 cells, with the single and double Ets-1 mutants leading to the same enhancement of a transcriptional response (Figure 6c). We also examined distinct Ets-dependent reporter genes, that is the E74-luc reporter vector which contains three Ets-binding sites and the ICAM-1-luc reporter vector in which transcription is directed from the human ICAM-1 promoter containing two Ets-binding sites (de Launoit et al, 1998). Enhancement of the transcriptional response using the double Ets-1 sumoylation mutant was observed for both reporter vectors (Figure 6d and data not shown).…”

Section: Sumoylation and Ubiquitinylation Of Ets-1mentioning

confidence: 97%

Regulation of the Ets-1 transcription factor by sumoylation and ubiquitinylation

Degerny

Vintonenko

et al. 2006

Oncogene

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Sumoylation and ubiquitinylation reversibly regulate the activity of transcription factors through covalent attachment to lysine residues of target proteins. We examined whether the Ets-1 transcription factor is modified by sumoylation and/or ubiquitinylation. Among four potential SUMO motifs in Ets-1, we identified lysines 15 and 227 within the LK 15 YE and IK 227 QE motifs, as being the sumoylation acceptor sites. Using transfection of Ets-1 wildtype (WT) or its sumoylation deficient version (Ets-1 K15R/K227R), as well as WT or mutant proteins of the SUMO pathway, we further demonstrated that the E2 SUMO-conjugating enzyme Ubc9 and a E3 SUMO ligase, PIASy, can enhance Ets-1 sumoylation, while a SUMO protease, SENP1, can desumoylate Ets-1. We also found that Ets-1 is modified by K48-linked polyubiquitinylation independently of the sumoylation acceptor sites and is degraded through the 26S proteasome pathway, while sumoylation of Ets-1 does not affect its stability. Finally, sumoylation of Ets-1 leads to reduced transactivation and we demonstrated that previously identified critical lysine residues in Synergistic Control motifs are the sumoylation acceptor sites of Ets-1. These data show that Ets-1 can be modified by sumoylation and/or ubiquitinylation, with sumoylation repressing transcriptional activity of Ets-1 and having no clear antagonistic action on the ubiquitin-proteasome degradation pathway.

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Section: Sumoylation and Ubiquitinylation Of Ets-1mentioning

confidence: 97%

Regulation of the Ets-1 transcription factor by sumoylation and ubiquitinylation

Degerny

Vintonenko

et al. 2006

Oncogene

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“…2B and Table I). ETV5, an activator of ICAM expression [20], was also present at higher protein levels in unstimulated AR BOECs nuclei than in nuclei of NAR or NS BOECs as determined by Western blots (see Fig. 3).…”

Section: Responses To Stimulimentioning

confidence: 99%

Proinflammatory phenotype with imbalance of KLF2 and RelA: Risk of childhood stroke with sickle cell anemia

et al. 2009

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Altered inflammation signaling within the cerebral vasculature may be an important risk factor for stroke in children with sickle cell anemia (SCA). This study examines how differential expression of NFjB/p65 (RelA), KLF2, and other transcription factors may act as switches in inflammation signaling leading to observed differences between non-SCA (NS) African Americans and African Americans with SCA who are either at risk (AR) or not at risk (NAR) of childhood stroke based on occurrence of Circle of Willis disease. Clover/ Transfac analysis was used to identify overrepresented transcription factor binding motifs on genes associated with inflammation. Transcription factor binding motifs for the NFjB family and RFX1 were overrepresented on inflammation signaling gene set analysis. Variations in protein expression were determined by flow cytometry of blood outgrowth endothelial cells (BOECs) from NS, AR, and NAR donors and Western blots of protein extracts from both unstimulated and TNFa/IL1b-stimulated BOECs. BOECs from patients with SCA had more cytoplasmic-derived RelA compared with NS BOECs. Sickle BOECs also had heightened responses to inflammatory stimuli compared with NS BOECs, as shown by increased nuclear RelA, and intracellular adhesion molecule (ICAM) response to TNFa/IL1b stimulation. Multiple control points in RelA signaling were associated with risk of childhood stroke. The ratio of proinflammatory factor RelA to anti-inflammatory factor KLF2 was greater in BOECs from AR donors than NS donors. Group risk of childhood stroke with SCA was greatest among individuals who exhibited increased expression of proinflammatory transcription factors and decreased expression of transcription factors that suppress inflammation. Am. J. Hematol. 85:18-23, 2010. V

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“…To analyze the effect of COP1 on ERM-induced transcriptional activity, we performed a luciferase reporter gene assay by using ERM and the ICAM-1 luciferase reporter plasmid previously identified as PEA3 group-responsive (de Launoit et al, 1998). As shown in Figure 3a, COP1 had no important effect on the basal ICAM-1 reporter transcription in RK13 cells.…”

Section: Cop1 Decreased Pea3 Group Member-induced Transcriptional Actmentioning

confidence: 99%

The E3 ubiquitin ligase complex component COP1 regulates PEA3 group member stability and transcriptional activity

et al. 2010

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In this study, we report that the PEA3 group members interact with the mammalian really interesting new gene (RING) E3 ubiquitin ligase constitutive photomorphogenetic 1 (COP1), which mediates ubiquitylation and subsequent proteasome degradation of the p53 and c-Jun transcription factors. This interaction is mediated by the central region of COP1 including the coiled-coil domain and two COP1-interacting consensus motifs localized in the well-conserved N-terminal transactivation domain of the PEA3 group members. At the transcriptional level, COP1 reduces the transcriptional activity of ERM and the two other PEA3 group proteins on Ets-responsive reporter genes; this effect being dependent on the RING domain of COP1 and the two COP1-interacting motifs of ERM. Reduced transcriptional activity was, however, not related to COP1-induced changes in ERM stability. In fact, increased ubiquitylation and subsequent proteasomemediated degradation of ERM is achieved only when COP1 is expressed with DET1, a key COP1 partner within the ubiquitylation complex. Conversely, we show that the depletion of COP1 or DET1 by small interference RNA (siRNA) in U2OS cells stabilizes endogenous ERM whereas only COP1 knockdown enhances expression of ICAM-1, a gene regulated by this transcription factor. These results indicate that COP1 is a complex regulator of ERM and the two other PEA3 group members.

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The transcription of the intercellular adhesion molecule-1 is regulated by Ets transcription factors

Cited by 60 publications

References 24 publications

Regulation of the Ets-1 transcription factor by sumoylation and ubiquitinylation

Regulation of the Ets-1 transcription factor by sumoylation and ubiquitinylation

Proinflammatory phenotype with imbalance of KLF2 and RelA: Risk of childhood stroke with sickle cell anemia

The E3 ubiquitin ligase complex component COP1 regulates PEA3 group member stability and transcriptional activity

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