IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
artículos
Título:
STAT1, STAT3 and p38MAPK are involved in the apoptotic effect induced by a chimeric cyclic interferon-a2b peptide
Autor/es:
VIVIANA BLANK, CLARA PEÑA, LEONOR ROGUIN
Revista:
EXPERIMENTAL CELL RESEARCH
Editorial:
ELSEVIER INC
Referencias:
Lugar: Irlanda; Año: 2009 vol. 316 p. 603 - 614
ISSN:
0014-4827
Resumen:
designed and synthesized a chimeric cyclic peptide of the IFN-á2b that inhibits WISH cell
proliferation by inducing an apoptotic response. Here, we first studied the ability of this peptide to
activate intracellular signaling pathways and then evaluated the participation of some signals in
the induction of apoptosis. Stimulation of WISH cells with the cyclic peptide showed tyrosine
phosphorylation of Jak1 and Tyk2 kinases, tyrosine and serine phosphorylation of STAT1 and
STAT3 transcription factors and activation of p38 MAPK pathway, although phosphorylation levels
or kinetics were in some conditions different to those obtained under IFN-á2b stimulus. JNK and
p44/42 pathways were not activated by the peptide in WISH cells.We also showed that STAT1 and
STAT3 downregulation by RNA interference decreased the antiproliferative activity and the
amount of apoptotic cells induced by the peptide. Pharmacological inhibition of p38 MAPK also
reduced the peptide growth inhibitory activity and the apoptotic effect. Thus, we demonstrated
that the cyclic peptide regulates WISH cell proliferation through the activation of Jak/STAT
signaling pathway. In addition, our results indicate that p38 MAPK may also be involved in cell
growth regulation. This study suggests that STAT1, STAT3 and p38 MAPK would be mediating the
antitumor and apoptotic response triggered by the cyclic peptide in WISH cells.
p44/42 pathways were not activated by the peptide in WISH cells.We also showed that STAT1 and
STAT3 downregulation by RNA interference decreased the antiproliferative activity and the
amount of apoptotic cells induced by the peptide. Pharmacological inhibition of p38 MAPK also
reduced the peptide growth inhibitory activity and the apoptotic effect. Thus, we demonstrated
that the cyclic peptide regulates WISH cell proliferation through the activation of Jak/STAT
signaling pathway. In addition, our results indicate that p38 MAPK may also be involved in cell
growth regulation. This study suggests that STAT1, STAT3 and p38 MAPK would be mediating the
antitumor and apoptotic response triggered by the cyclic peptide in WISH cells.
proliferation by inducing an apoptotic response. Here, we first studied the ability of this peptide to
activate intracellular signaling pathways and then evaluated the participation of some signals in
the induction of apoptosis. Stimulation of WISH cells with the cyclic peptide showed tyrosine
phosphorylation of Jak1 and Tyk2 kinases, tyrosine and serine phosphorylation of STAT1 and
STAT3 transcription factors and activation of p38 MAPK pathway, although phosphorylation levels
or kinetics were in some conditions different to those obtained under IFN-á2b stimulus. JNK and
p44/42 pathways were not activated by the peptide in WISH cells.We also showed that STAT1 and
STAT3 downregulation by RNA interference decreased the antiproliferative activity and the
amount of apoptotic cells induced by the peptide. Pharmacological inhibition of p38 MAPK also
reduced the peptide growth inhibitory activity and the apoptotic effect. Thus, we demonstrated
that the cyclic peptide regulates WISH cell proliferation through the activation of Jak/STAT
signaling pathway. In addition, our results indicate that p38 MAPK may also be involved in cell
growth regulation. This study suggests that STAT1, STAT3 and p38 MAPK would be mediating the
antitumor and apoptotic response triggered by the cyclic peptide in WISH cells.
p44/42 pathways were not activated by the peptide in WISH cells.We also showed that STAT1 and
STAT3 downregulation by RNA interference decreased the antiproliferative activity and the
amount of apoptotic cells induced by the peptide. Pharmacological inhibition of p38 MAPK also
reduced the peptide growth inhibitory activity and the apoptotic effect. Thus, we demonstrated
that the cyclic peptide regulates WISH cell proliferation through the activation of Jak/STAT
signaling pathway. In addition, our results indicate that p38 MAPK may also be involved in cell
growth regulation. This study suggests that STAT1, STAT3 and p38 MAPK would be mediating the
antitumor and apoptotic response triggered by the cyclic peptide in WISH cells.
á2b that inhibits WISH cell
proliferation by inducing an apoptotic response. Here, we first studied the ability of this peptide to
activate intracellular signaling pathways and then evaluated the participation of some signals in
the induction of apoptosis. Stimulation of WISH cells with the cyclic peptide showed tyrosine
phosphorylation of Jak1 and Tyk2 kinases, tyrosine and serine phosphorylation of STAT1 and
STAT3 transcription factors and activation of p38 MAPK pathway, although phosphorylation levels
or kinetics were in some conditions different to those obtained under IFN-á2b stimulus. JNK and
p44/42 pathways were not activated by the peptide in WISH cells.We also showed that STAT1 and
STAT3 downregulation by RNA interference decreased the antiproliferative activity and the
amount of apoptotic cells induced by the peptide. Pharmacological inhibition of p38 MAPK also
reduced the peptide growth inhibitory activity and the apoptotic effect. Thus, we demonstrated
that the cyclic peptide regulates WISH cell proliferation through the activation of Jak/STAT
signaling pathway. In addition, our results indicate that p38 MAPK may also be involved in cell
growth regulation. This study suggests that STAT1, STAT3 and p38 MAPK would be mediating the
antitumor and apoptotic response triggered by the cyclic peptide in WISH cells.
p44/42 pathways were not activated by the peptide in WISH cells.We also showed that STAT1 and
STAT3 downregulation by RNA interference decreased the antiproliferative activity and the
amount of apoptotic cells induced by the peptide. Pharmacological inhibition of p38 MAPK also
reduced the peptide growth inhibitory activity and the apoptotic effect. Thus, we demonstrated
that the cyclic peptide regulates WISH cell proliferation through the activation of Jak/STAT
signaling pathway. In addition, our results indicate that p38 MAPK may also be involved in cell
growth regulation. This study suggests that STAT1, STAT3 and p38 MAPK would be mediating the
antitumor and apoptotic response triggered by the cyclic peptide in WISH cells.
á2b stimulus. JNK and
p44/42 pathways were not activated by the peptide in WISH cells.We also showed that STAT1 and
STAT3 downregulation by RNA interference decreased the antiproliferative activity and the
amount of apoptotic cells induced by the peptide. Pharmacological inhibition of p38 MAPK also
reduced the peptide growth inhibitory activity and the apoptotic effect. Thus, we demonstrated
that the cyclic peptide regulates WISH cell proliferation through the activation of Jak/STAT
signaling pathway. In addition, our results indicate that p38 MAPK may also be involved in cell
growth regulation. This study suggests that STAT1, STAT3 and p38 MAPK would be mediating the
antitumor and apoptotic response triggered by the cyclic peptide in WISH cells.