Mañana, JUEVES, 24 DE ABRIL, el sistema se apagará debido a tareas habituales de mantenimiento a partir de las 9 de la mañana. Lamentamos las molestias.
Regulación de la transcripción de la interleuquina 2 en linfocitos T: proteínas quinasas implicadas en la regulación de la capacidad de transactivación de NF-kB y NFAT
Advisor
Fresno Escudero, ManuelEntity
UAM. Departamento de Biología MolecularDate
2005-06-15Subjects
Proteínas quinasas - Tesis doctorales; Linfocitos T - Tesis doctorales; Interleukina 2 - Tesis doctorales; Biología y Biomedicina / BiologíaNote
Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 15-06-2005Abstract
Signals through the T cell receptor (TcR) are not enough to provide a full stimulation of T cells. Additional costimulatory signals are required. CD28 engagement iii T cells provides a synergistic stimulation with the TcR resulting in the activation of NFAT, NF-KB and AP-1 transcription factors, required for cytokine production and cell proliferation.
Our results supports that NIK nlay be controlling IL-2 transcription and T cell activation by modulating c-Rel phosphorylation in specific serines of the transactivation doinain (TAD). This leads to a niore efficient transactivation of genes which are dependen1 on CD28RE sites where c-Re1 binds such IL-2 and CM-CSF promoters. According with this, we have observed a similar behavior of T cells
activation harboring c-Rel mutatioiis (Jurkat D6 and mutant deficient in c-Rel) or ciíy/c~íy mice (that have a defective NIK protein).
On the other Iiand, postraiiscriptional modifications are increasingly recognized as iiiiportant way to modulate NF-KB and NFAT activity. This regulation involves the signal-depcndent phosphorylation and activation of tlie TADs by various kinases. We show that protein kiiiase C (PKC)<, Cot kinase and NIK, which have been previously
shown to activate NF-KB, are also iiivolved in regulating the transactivation function of c-Rel, p65 y NFATc2 in T cells. Cot induction of c-Re1 and NFATc2 transactivating activity seem to be mediated sequentially through PKCr and NIK activation. Moreover,
mutation of several serines, including Ser 471, in the transactivation domain (TAD) of c-Rel abrogated NIK and Cot enhancing activity of its transactivating activity. In contrasts, NIK regulates p65 TAD in an independent pathway to Cot/PKC<.
Those results shed light to an important aspect of regulation of the
transactivation activity of rapid response transcription factor.
Files in this item
Size
3.005Mb
Format
PDF
Description
Texto de la Tesis Doctoral
Google Scholar:Sánchez-Valdepeñas Villegas, Carmen
This item appears in the following Collection(s)
Related items
Showing items related by title, author, creator and subject.
-
Estudio del receptor de interleuquina 2: regulación transcripcional del componente [alfa] por glucocorticoides
Sanz Merino, Eva María
1991-04-16