Relations structure-fonction de Erm, un membre du groupe PEA3 appartenant à la famille des facteurs de transcription ETS

La grande famille des facteurs de transcription Ets est caractérisée par un domaine de liaison à l’ADN, le domaine ETS, qui présente une structure de type hélice-tour-hélice ailé et qui reconnaît la séquence nucléotidique GGAA/T. Ces facteurs sont des protéines modulaires, dont les domaines sont structurellement conservés, régulent la transcription de leurs gènes cibles. L’action régulatrice de ces facteurs de transcription, ainsi que leur spécificité, dépendent de leurs sites d’expression, du taux auquel ils sont exprimés ainsi que des modifications post-traductionnelles qui les touchent. Au sein de la famille Ets, les trois membres du groupe PEA3 - Erm, Pea3 et Er81 - sont impliqués dans divers processus tant physiologiques tels que le développement des neurones sensitifs et moteurs que pathologiques tels que la croissance et l’invasion tumorale ou l’apparition de métastases, au niveau mammaire notamment.Notre travail a eu pour ambition de mieux comprendre les relations structure/fonction des membres du groupe PEA3, et plus particulièrement de Erm. \Doctorat en sciences biomédicalesinfo:eu-repo/semantics/nonPublishe

The 26S proteasome system degrades the ERM transcription factor and regulates its transcription-enhancing activity

ERM is a member of the ETS transcription factor family. High levels of the corresponding mRNA are detected in a variety of human breast cancer cell lines, as well as in aggressive human breast tumors. As ERM protein is almost undetectable in these cells, high degradation of this transcription factor has been postulated. Here we have investigated whether ERM degradation might depend on the proteasome pathway. We show that endogenous and ectopically expressed ERM protein is short-lived protein and undergoes proteasome-dependent degradation. Deletion mutagenesis studies indicate that the 61 C-terminal amino acids of ERM are critical for its proteolysis and serve as a degradation signal. Although ERM conjugates with ubiquitin, this post-translational modification does not depend on the C-terminal domain. We have used an Ets-responsive ICAM-1 reporter plasmid to show that the ubiquitin-proteasome pathway can affect transcriptional function of ERM. Thus, ERM is subject to degradation via the 26S proteasome pathway, and this pathway probably plays an important role in regulating ERM transcriptional activity. © 2007 Nature Publishing Group. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

The Ets transcription factors of the PEA3 group: Transcriptional regulators in metastasis

The PEA3 group is composed of three highly conserved Ets transcription factors: Erm, Er81, and Pea3. These proteins regulate transcription of multiple genes, and their transactivating potential is affected by post-translational modifications. Among their target genes are several matrix metalloproteases (MMPs), which are enzymes degrading the extracellular matrix during normal remodelling events and cancer metastasis. In fact, PEA3-group genes are often over-expressed in different types of cancers that also over-express these MMPs and display a disseminating phenotype. Experimental regulation of the synthesis of PEA3 group members influences the metastatic process. This suggests that these factors play a key role in metastasis. © 2006 Elsevier B.V. All rights reserved.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Expression of the Ets transcription factor Erm is regulated through a conventional PKC signaling pathway in the Molt4 lymphoblastic cell line.

Erm, a member of the PEA3 group within the Ets family of transcription factors, is expressed in murine and human lymphocytes. Here, we show that in the human Molt4 lymphoblastic cell line, the erm gene expression is regulated by the conventional PKC (cPKC) pathway. To better characterize the molecular mechanism by which cPKC regulates Erm transcription in Molt4 cells, we tested proximal promoter deletions of the human gene, and identified a specific cPKC-regulated region between positions -420 and -115 upstream of the first exon.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Les facteurs de transcription du groupe PEA3: Régulateurs transcriptionnels dans le processus de cancérisation

Erm, Er81, and Pea3 are the three members of the PEA3 group which belong to the Ets transcription factors family. These proteins regulate transcription of multiple target genes, such as those encoding several matrix metalloproteinases (MMP), which are enzymes degrading the extracellular matrix during cancer metastasis. In fact, PEA3-group genes are often overexpressed in different types of human cancers that also over-express these MMP and display a disseminating phenotype. In experimental models, regulation of PEA3 group member expression has been shown to influence the metastatic process, thus suggesting that these factors play a key role in metastasis. © John Libbey Eurotext.SCOPUS: re.jinfo:eu-repo/semantics/publishe