RESUMO
Twist proteins are members of basic helix-loop-helix family and are major regulators of embryogenesis. In adult humans, Twist proteins are mainly expressed in precursor cells, including myogenic, osteoblastic, chondroblastic and myelomonocytic lineages, maintaining their undifferentiated state. In addition, they play important roles in lymphocyte function and maturation. Recently, several studies have reported regulatory roles for Twist in the function and development of hematopoietic cells as well as in survival and development of numerous hematological malignancies. It is activated by numerous signal transduction pathways, including Akt, nuclear factor κB, Wnt, signal transducer and activator of transcription 3, mitogen-activated protein kinase and Ras signaling. Activated Twist has an anti-apoptotic role and protects cancer cells from apoptotic cell death. In addition, overexpression of Twist promotes the process of epithelial-mesenchymal transition, which has an essential role in cancer metastasis. Hereby, we review the aberrant expression of Twist in hematopoietic malignancies such as leukemias, lymphomas and myelodysplastic syndrome, which is related with poor prognosis and drug resistance in these disorders. Inactivation of Twist by small RNAs technology or chemotherapeutic inhibitors targeting Twist and upstream or downstream molecules of Twist signaling pathways may be helpful in management of disease to improve treatment strategies in malignancies (AU)
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Assuntos
Humanos , Masculino , Feminino , Biomarcadores/metabolismo , Neoplasias da Medula Óssea/metabolismo , Neoplasias da Medula Óssea/patologia , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/genética , Protamina Quinase/administração & dosagem , Epitélio/anormalidades , Leucemia/sangue , Nicho de Células-Tronco/genética , Biomarcadores/análise , Neoplasias da Medula Óssea/complicações , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patologia , Protamina Quinase , Protamina Quinase/metabolismo , Apoptose/fisiologia , Epitélio/patologia , Leucemia/tratamento farmacológico , Nicho de Células-Tronco/fisiologiaRESUMO
G protein-coupled receptor kinase 2 (GRK2) emerges as a key modulator of G protein-coupled receptors and other plasma membrane receptors triggered by chemotactic messengers. In addition, GRK2 has been reported to interact with a variety of signal transduction proteins related to cell migration. Interestingly, the levels of expression and activity of this kinase are altered in several inflammatory disorders, thus suggesting that it may play an important role in the onset or progression of these pathologies. This review summarizes the mechanisms involved in the control of GRK2 expression and function and highlights novel functional interactions of this protein that might help to explain how altered GRK2 levels affects cell migration in different cell types and pathological settings (AU)
La quinasa GRK2 (G protein-coupled receptor kinase 2) se perfila como un modulador clave de receptores acoplados a proteínas G y de otros receptores de membrana plasmática que responden a estímulos migratorios. Además, GRK2 es capaz de interaccionar con diferentes proteínas señalizadoras relacionadas con la migración celular. Por otra parte, puesto que los niveles de expresión y actividad de esta quinasa se encuentran alterados en distintas en enfermedades inflamatorias, se sugiere que GRK2 puede desempeñar un papel importante en el desencadenamiento o la progresión de estos procesos. Esta revisión resume los mecanismos implicados en el control de la expresión y función de GRK2 y resalta nuevas interacciones funcionales de esta proteína que pueden contribuir a explicar cómo las alteraciones en los niveles de GRK2 afectan a la migración de distintos tipos celulares y a diversas situaciones patológicas (AU)
