Functional characterization of the protein and its role in cellular proliferation and leukemogenesis

• Processo: 07/54870-5
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Data de Início da vigência: 01 de maio de 2008
• Data de Término da vigência: 30 de abril de 2011
• Área do conhecimento: Ciências da Saúde - Medicina - Clínica Médica
• Acordo de Cooperação: DFG
• Pesquisador responsável: Sara Teresinha Olalla Saad
• Beneficiário: Sara Teresinha Olalla Saad
• Pesquisador Responsável no exterior: Stefan K. Bohlander
• Instituição Parceira no exterior: Ludwig Maximilian University of Munich (LMU Munich), Alemanha
• Instituição Sede: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brasil
• Bolsa(s) vinculada(s): 10/15588-5 - Caracterização funcional da proteína CATS e sua participação na proliferação celular e na leucemogênese, BP.TT
• Assunto(s): Proliferação celular Repetição de anquirina Síndromes mielodisplásicas
• Palavra(s)-Chave do Pesquisador: Ankhd1 | Cats | Leukamogenesis | Myelodysplasia | Siva

Resumo

CATS is the CALM (PICALM) interacting protein expressed in thymus and spleen. The CATS interaction region of CALM is contained in the leukemogenic fusion protein CALM/AF10, which is found in AML, ALL and in malignant lymphoma. CATS sequesters CALM/AF10 in the nucleolus and interferes with the transactivation capacity of CALM/AF10 in a dose-dependent manner. However, the involvement of CATS in malignant transformation seems to go beyond its interaction with the CALM/AF10. CATS is highly expressed in leukemia, lymphoma and tumor cell lines but not in non-proliferating T-cells or PBLs. Protein levels are cell cycle-dependem and induced by mitogens (e.g. PHA). The upregulation of CATS upon mitogenic activation and its high expression in proliferating but not in quiescent cells, as well as its nucleolar localization, suggest a role of CATS in the control of cell proliferation. Several CATS interacting proteins were identified, including SIVA-1, a pro-apoptotic protein. Recently, we have shown that SIVA-1 also associates with ANKHD1 (Ankyrin Repeat and KH domain containing 1). Similarly to CATS, ANKHD1 is highly expressed in leukemia cell lines suggesting a role for this protein in leukemogenesis. The fact that CATS and ANKHD1 are highly expressed in leukemia cell lines and are both involved in protein interaction with SIVA-1, indicate that these proteins might be involved in the same regulatory pathway contributing to malignant transformation. The aim of this project is to investigate to which extent CATS contributes to or determines cell proliferation and what effect its depletion or overexpression might have on myelodysplastic, leukemic and tumor cells. Moreover we aim to analyze CATS interaction with its partner proteins. This work will provide valuable insights into regulatory networks in which CATS might be involved and that are key pathways involved in tumorigenesis. (AU)

Publicações científicas

(4)

(Referências obtidas automaticamente do Web of Science e do SciELO, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores)

ARCHANGELO, LETICIA FROEHLICH; GREIF, PHILIPP A.; MAUCUER, ALEXANDRE; MANCEAU, VALERIE; KONERU, NARESH; BIGARELLA, CAROLINA L.; NIEMANN, FERNANDA; DOS SANTOS, MARCOS TADEU; KOBARG, JOERG; BOHLANDER, STEFAN K.; et al. The CATS (FAM64A) protein is a substrate of the Kinase Interacting Stathmin (KIS). BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v. 1833, n. 5, p. 1269-1279, MAY 2013. (07/08019-1, 07/54870-5)

LANARO, C.; FRANCO-PENTEADO, C. F.; ALBUQUEQUE, D. M.; SAAD, S. T. O.; CONRAN, N.; COSTA, F. F.. Altered levels of cytokines and inflammatory mediators in plasma and leukocytes of sickle cell anemia patients and effects of hydroxyurea therapy. Journal of Leukocyte Biology, v. 85, n. 2, p. 235-242, Feb. 2009. (08/57895-1, 07/50853-9, 07/54870-5)

BIGARELLA, CAROLINA L.; VIEIRA FERRO, KARLA P.; BARCELLOS, KARIN S. A.; MARTINS-DE-SOUZA, DANIEL; TRAINA, FABIOLA; NOVELLO, JOSE C.; OLALLA SAAD, SARA T.; ARCHANGELO, LETICIA FROEHLICH. Post-translational modification of the RhoGTPase activating protein 21, ARHGAP21, by SUMO2/3. FEBS Letters, v. 586, n. 19, p. 3522-3528, SEP 21 2012. (07/08019-1, 07/54870-5, 09/07322-8)

ARCHANGELO, LETICIA FROEHLICH; GREIF, PHILIPP A.; HOELZEL, MICHAEL; HARASIM, THOMAS; KREMMER, ELISABETH; PRZEMECK, GERHARD K. H.; EICK, DIRK; DESHPANDE, ANIRUDDHA JAYANT; BUSKE, CHRISTIAN; DE ANGELIS, MARTIN HRABE; et al. The CALM and CALM/AF10 interactor CATS is a marker for proliferation. MOLECULAR ONCOLOGY, v. 2, n. 4, p. 356-367, DEC 2008. (07/08019-1, 07/54870-5)