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Nom du laboratoire |
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Accueil FRE
2944 - Equipe 1
- Equipe 2 - Equipe
3 - Equipe 4 |
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Equipe 3 |
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Responsable :
Irina Groisman |
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Personne à contacter pour information : Nom : Irina Groisman Tél : 01 49-58-34-01 Email : Irina.Groisman@gmail.com |
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Effectif chercheurs et enseignants-chercheurs : Inserm : SR1 |
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Résumé scientifique de l’équipe : Background Translation is now recognized as an important regulatory step allowing direct, rapid, reversible, and localized control of protein levels during various physiological and pathological conditions. The regulatory sequences governing translational regulations of the mRNAs are located in their 3’untranslated regions. The best characterized of these sequences is the cytoplasmic polyadenylation element (CPE). The CPE is bound by CPE binding protein (CPEB), a conserved RNA binding protein that controls length of poly-A tail during early development, cell-cycle and synapse formation. The Xp54 RNA helicase was found to associate with CPEB in both Spisula and Xenopus. Depletion of Dhh1p, the yeast homolog of p54, elicits a reduction in the cell’s ability to repress translation. This translational repression was also dependent on proper P-body formation. Initially, P-bodies were suggested as sites for mRNA degradation, but recently they were also implicated in mRNA storage. Overexpression of CPEB in mammalian cells increases P-body foci. Recent findings that mRNAs translationally repressed by miRNAs accumulating in P-bodies suggest that miRNA-based translational repression components might also interact with this general translational repression machinery. Moreover, miRNA target mRNAs are subject to deadenylation, supporting an idea that the length of poly-A tail is one of the key elements in the control of the translation efficiency. Recently it was found that CPEB is important for cellular senescence. MEFs (mouse embryonic fibroblasts) derived from CPEB KO mice are immortal unlike wild type MEFs that do senesce. This suggests a role of CPEB in cancer and aging, and points toward importance of further investigation of CPEB role in mammalian cells, especially during cancer transformation. Aims Explore molecular mechanisms of CPEB-dependent translational regulation in mammalian cells. My preliminary data shows a few miRNAs (e.g., mir-15b) can work with CPEB during translation inhibition of mRNA. c-Myc and Wee1 mRNAs are potential targets for both mir-15b and CPEB. I will verify whether CPEB collaborates with miRNA in translational inhibition by using luciferase reporter assay. I will also investigate correlation of CPEB dependent translational inhibition and its localization in P-bodies. Investigate CPEB-dependent translational regulation during cancer transformation. My preliminary data shows that most of organs contain 20-50% less CPEB mRNA in cancer tissues compared to the normal ones. Surprisingly, two types of tumors, melanoma and seminoma, have 2-5 times more CPEB mRNA in comparison to normal skin and testis I will explore if CPEB is involved in prevention of cancer transformation (breast cancer) or its induction (melanoma) and will search for specific CPEB mRNA targets and miRNA-colaborators. |
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Sélection de publications 2005-2009 (<10) : 1.
Groisman, I., Ivshina, M., Marin, V., Kennedy, N.J., Davis, R.J. and
Richter, J.D. Control of Cellular Senescence by CPEB Gene Dev. 2006, v.20,
p.2701-12 2.
Groisman, I., Jung, M-Y., Sarkissian, M., Cao, Q. and Richter, J.D.
Translational control of the Embryonic Cell Cycle. Cell. 2002, v.109,
p.473-483 3.
Groisman I., Huang, Y-S., Mendez, R., Cao, Q., Theurkauf, W. and
Richter, J.D. CPEB, Maskin, and Cyclin B1 mRNA at the Mitotic Apparatus:
Implications for local translational control of cell division. Cell. 2000,
v.103, p. 435-447. 4.
Groisman, I., Huang, Y-S., Mendez, R., Cao, Q. and Richter, J. D.
Translational control of Embryonic Cell Division by CPEB and Maskin. Cold
Spring Harbor Symposium of Qvantitative Biology "The Ribosome". 2001, v.66,
p.345-351 |
