TITLE

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

AUTHOR(S)

Ji, Z.; Degerny, C.; Vintonenko, N.; Deheuninck, J.; Foveau, B.; Leroy, C.; Coll, J.; Tulasne, D.; Baert, J.-L.; Fafeur, V.

PUB. DATE

January 2007

SOURCE

Oncogene;1/18/2007, Vol. 26 Issue 3, p395

SOURCE TYPE

Academic Journal

DOC. TYPE

Article

ABSTRACT

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 LK15YE and IK227QE 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.Oncogene (2007) 26, 395–406. doi:10.1038/sj.onc.1209789; published online 24 July 2006

ACCESSION #

23717154

 

Related Articles

• The Reconstruction of Condition-Specific Transcriptional Modules Provides New Insights in the Evolution of Yeast AP-1 Proteins. Goudot, Christel; Etchebest, Catherine; Devaux, Frédéric; Lelandais, Gaëlle // PLoS ONE;2011, Vol. 6 Issue 6, p1 

  AP-1 proteins are transcription factors (TFs) that belong to the basic leucine zipper family, one of the largest families of TFs in eukaryotic cells. Despite high homology between their DNA binding domains, these proteins are able to recognize diverse DNA motifs. In yeasts, these motifs are...

• Inferring protein DNA dependencies using motif alignments and mutual information. Shaun Mahony; Philip E. Auron; Panayiotis V. Benos // Bioinformatics;Jul2007, Vol. 23 Issue 13, pi297 

  Motivation: Mutual information can be used to explore covarying positions in biological sequences. In the past, it has been successfully used to infer RNA secondary structure conformations from multiple sequence alignments. In this study, we show that the same principles allow the discovery of...

• The MEKK1 SWIM domain is a novel substrate receptor for c-Jun ubiquitylation. RIEGER, Michael A.; DUELLMAN, Tyler; HOOPER, Christopher; AMEKA, Magdalene; BAKOWSKA, Joanna C.; CUEVAS, Bruce D. // Biochemical Journal;8/15/2012, Vol. 446 Issue 1, p431 

  MEKK1 [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase kinase 1] is a MAP3K (MAPK kinase kinase) that regulates MAPK activation, and is the only known mammalian kinase that is also a ubiquitin ligase. MEKK1 contains a RING domain within its N-terminal...

• The HMG-box: a versatile protein domain occurring in a wide variety of DNA-binding proteins. Štros, M.; Launholt, D.; Grasser, K. D. // Cellular & Molecular Life Sciences;Oct2007, Vol. 64 Issue 19/20, p2590 

  The HMG-box domain of ~75 amino acid residues was originally identified as the domain that mediates the DNA-binding of chromatin-associated high-mobility group (HMG) proteins of the HMGB type. In the last few years, HMG-box domains have been found in various DNA-binding proteins including...

• Constitutive expression of the DNA-binding domain of Ets1 increases endothelial cell adhesion and stimulates their organization into capillary-like structures. Mattot, Virginie; Vercamer, Chantal; Soncin, Fabrice; Calmels, Thierry; Huguet, Christelle; Fafeur, Véronique; Vandenbunder, Bernard // Oncogene;2/10/2000, Vol. 19 Issue 6, p762 

  We previously reported that the Ets1 transcription factor is expressed in endothelial cells during angiogenesis both in normal and pathological development. We analyse here the effects of the stable expression of an Ets transdominant negative mutant (Ets1-DB), consisting in an Ets1 protein...

• In-silico Study of Transcription Factor Binding Elements of Human PAX Gene Family Members. Rashmi; Singh, V. K.; Gangopadhyay, A. N.; Shah, G. L.; Khanna, A.; Mohapatra, T. M.; Shankar, Om; Singh, Royana // Trends in Bioinformatics;2013, Vol. 6 Issue 3, p62 

  PAX gene family members, tissue specific transcription factors mainly involved in the formation of tissues and organs during embryonic development and has important role in transcriptional regulation. The presence of consensus paired domain play significant role in DNA-binding transcription...

• A Full-Length Dof1 Transcription Factor of Finger Millet and its Response to a Circadian Cycle. Kumar, Anil; Kanwal, Pooja; Gupta, Alok; Singh, B.; Gaur, Vikram // Plant Molecular Biology Reporter;Apr2014, Vol. 32 Issue 2, p419 

  DOF1 (DNA binding with one finger) plays an important role in regulating C/N metabolism in cereals. In order to validate its role in the regulation of nitrogen use efficiency (NUE) and photosynthetic efficiency in finger millet, 5′-3′ RACE PCR was performed to obtain and characterize...

• Transcriptional Activation Domain of Human BTEB2, A GC Box-Binding Factor1. Kojima, Satoshi; Kobayashi, Akira; Gotoh, Osamu; Ohkuma, Yoshiaki; Fujii-Kuriyama, Yoshiaki; Sogawa, Kazuhiro // Journal of Biochemistry;1997, Vol. 121 Issue 2, p389 

  BTEB2 is a GC box-binding transcription factor containing proline-rich and zinc finger domains as transactivation and DNA binding domains, respectively. We have identified a small region in the proline-rich domain indispensable for its transcription-enhancing activity by transfection experiments...

• A point mutation in the DNA-binding domain of HPV-2 E2 protein increases its DNA-binding capacity and reverses its transcriptional regulatory activity on the viral early promoter.  // BMC Molecular Biology;2012, Vol. 13 Issue 1, p5 

  The article presents a study focusing on how point mutation in the DNA-binding domain of HPV-2 E2 protein increases its DNA-binding capacity. It also shows how point mutation reverses the transcriptional regulatory activity of the HPV-2 E2 protein on the viral early promoter. As stated, the...

Read the Article