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Doctoral Thesis
DOI
10.11606/T.42.2014.tde-26062014-182954
Document
Author
Full name
Christiane Bezerra de Araujo
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2014
Supervisor
Committee
Ferro, Emer Suavinho (President)
Kimura, Edna Teruko
Porcionatto, Marimelia Aparecida
Prado, Marcella Barbosa Faria de Almeida
Scavone, Cristoforo
Title in Portuguese
Novo peptídeo intracelular derivado da ciclina D2 induz morte celular.
Keywords in Portuguese
Apoptose
Ciclo celular
Morte celular
Necrose
Peptídeos intracelulares
Abstract in Portuguese
Peptídeos intracelulares são constantemente produzidos pelo sistema ubiquitina proteassomo e muitos são provavelmente funcionais. Aqui, um nonapeptídio derivado da ciclina-D2, específica da transição G1/S, chamado "pep5" mostrou um aumento específico durante a fase S do ciclo celular em células HeLa. O pep5 (50-100 μM) induziu a morte celular em células HeLa e em várias outras células tumorais, mas isso só ocorreu quando o pep5 foi sintetizado acoplado ao peptídeo penetrador de células (pep5-cpp). In vivo, o pep5-cpp reduziu o volume do glioblastoma C6 de ratos Wistar em cerca de 50%. A acetilação reduziu a potência do pep5-cpp, enquanto substituições Leu-Ala aboliram totalmente a atividade deste peptídeo. Os resultados de caracterização inicial do mecanismo de morte celular indizida pelo pep5 incluem ativação de caspases 3/7 e 9, inibição da fosforilação Akt2 e inibição da atividade do proteassomo. Esses dados colaboram com a hipótese da função de peptídeos intracelulares na sinalização.
Title in English
A novel intracellular peptide derived from cyclin D2 induces cell death.
Keywords in English
Apoptosis
Cell cycle
Cell death
Intracellular peptides
Necrosis
Abstract in English
Intracellular peptides are constantly produced by the ubiquitinproteasome system and many are probably functional. Here, a nonapeptide of G1/S-specific cyclin-D2 named pep5 showed a specific increase during the S phase of HeLa cell cycle. Pep5 (50-100 μM) induced cell death in HeLa and in several other tumor cells, only when it was fused to a cell penetrating peptide (pep5-cpp). In vivo, the pep5-cpp reduced the volume of the rat C6 glioblastoma by almost 50%. Acetylation reduced the potency of the pep5-cpp while Leu-Ala substitutions totally abolished the pep5 activity. Findings from the initial characterization of the cell death mechanism of pep5 include caspase 3/7 and 9 activation, inhibition of Akt2 phosphorylation and inhibition of proteasome activity. These data further support the intracellular function of peptides.
 
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Publishing Date
2014-06-27
 
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