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Targeting carcinogenesis: a role for the prolyl isomerase Pin1?
Lu, Kun Ping; Suizu, Futoshi; Zhou, Xiao Zhen; Finn, Greg; Lam, Prudence; Wulf, Gerburg.
Afiliación
  • Lu KP; Department of Medicine, Cancer Biology Program, Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA.
Mol Carcinog ; 45(6): 397-402, 2006 Jun.
Article en En | MEDLINE | ID: mdl-16652378
Phosphorylation of proteins on serine or threonine residues that immediately precede proline (pSer/Thr-Pro) is a central signaling mechanism in cell proliferation and transformation. Recent studies indicate that certain pSer/Thr-Pro motifs in native proteins exist in two completely distinct conformations, cis and trans, whose conversion is markedly slowed down upon phosphorylation, but specifically catalyzed by the peptidyl-prolyl cis/trans isomerase Pin1. Importantly, such Pin1-catalyzed conformational changes can have profound effects on the function of many phosphorylation signaling pathways, thereby playing an important role in various cellular processes. Moreover, increasing evidence indicates that aberrant Pin1 function plays an important role in the pathogenesis of some human diseases. Notably, Pin1 is not only overexpressed in a large number of human cancers, but also is an excellent prognostic marker in some cancers. Furthermore, Pin1 overexpression can function as a critical catalyst that amplifies multiple oncogenic signaling pathways during oncogenesis. Moreover, Pin1 overexpression causes cell transformation, centrosome amplification, genomic instability, and tumor development. In contrast, Pin1 knockout in mice prevents certain oncogenes from inducing tumors and Pin1 inhibition in cancer cells suppresses their cell proliferation, transformed phenotype and tumorigenicity in nude mice as well as increases the response to other anticancer agents. These results suggest that Pin1-mediated postphosphorylation regulation may provide a unique opportunity for disrupting oncogenic pathways, and thereby represent an appealing target for novel anticancer therapies.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transformación Celular Neoplásica / Isomerasa de Peptidilprolil Límite: Humans Idioma: En Revista: Mol Carcinog Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2006 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transformación Celular Neoplásica / Isomerasa de Peptidilprolil Límite: Humans Idioma: En Revista: Mol Carcinog Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2006 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos