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The CATS (FAM64A) protein is a substrate of the Kinase Interacting Stathmin (KIS)

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Archangelo, Leticia Froehlich [1] ; Greif, Philipp A. [2, 3] ; Maucuer, Alexandre [4] ; Manceau, Valerie [4] ; Koneru, Naresh [2, 3] ; Bigarella, Carolina L. [1] ; Niemann, Fernanda [1] ; dos Santos, Marcos Tadeu [5] ; Kobarg, Joerg [5] ; Bohlander, Stefan K. [2, 3, 6] ; Olalla Saad, Sara Teresinha [1]
Número total de Autores: 11
Afiliação do(s) autor(es):
[1] State Univ Campinas UNICAMP, Hematol & Hemotherapy Ctr, BR-13083878 Campinas, SP - Brazil
[2] Univ Munich, Dept Med 3, D-81377 Munich - Germany
[3] Helmholtz Zentrum Munchen, Clin Cooperat Grp Leukemia, Natl Res Ctr Environm Hlth, D-81377 Munich - Germany
[4] Inst Fer Moulin, INSERM, U839, F-75005 Paris - France
[5] Natl Ctr Res Energy & Mat CNPEM, Natl Lab Biosci LNBio, BR-13083970 Campinas, SP - Brazil
[6] Univ Marburg, Ctr Human Genet, Marburg - Germany
Número total de Afiliações: 6
Tipo de documento: Artigo Científico
Citações Web of Science: 8

The CATS protein (also known as FAM64A and RCS1) was first identified as a novel CALM (PICALM) interactor that influences the subcellular localization of the leukemogenic fusion protein CALM/AF10. CATS is highly expressed in cancer cell lines in a cell cycle dependent manner and is induced by mitogens. CATS is considered a marker for proliferation, known to control the metaphase-to-anaphase transition during the cell division. Using CATS as a bait in a yeast two-hybrid screen we identified the Kinase Interacting Stathmin (MS or UHMK1) protein as a CATS interacting partner. The interaction between CATS and KIS was confirmed by GST pull-down, co-immunopreciptation and co-localization experiments. Using kinase assay we showed that CATS is a substrate of KIS and mapped the phosphorylation site to CATS serine 131 (S131). Protein expression analysis revealed that KIS levels changed in a cell cycle-dependent manner and in the opposite direction to CATS levels. In a reporter gene assay KIS was able to enhance the transcriptional repressor activity of CATS, independent of CATS phophorylation at S131. Moreover, we showed that CATS and KIS antagonize the transactivation capacity of CALM/AF10.In summary, our results show that CATS interacts with and is a substrate for KIS, suggesting that KIS regulates CATS function. (c) 2013 Elsevier B.V. All rights reserved. (AU)

Processo FAPESP: 07/54870-5 - Functional characterization of the protein and its role in cellular proliferation and leukemogenesis
Beneficiário:Sara Teresinha Olalla Saad
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 07/08019-1 - Caracterização funcional da proteína CATS e sua participação na proliferação celular e na gênese da leucemia
Beneficiário:Leticia Fröhlich Archangelo
Linha de fomento: Bolsas no Brasil - Pós-Doutorado