Artículos de revistas
MAP kinase phosphatase-3 (MKP-3) is transcriptionally and post-translationally up-regulated by hCG and modulates cAMP-induced p21 expression in MA-10 Leydig cells
Fecha
2013-07Registro en:
Mori Sequeiros Garcia, Mercedes; Gómez, Natalia; Gorostizaga, Alejandra Beatriz; Acquier, Andrea Beatriz; González Calvar, Silvia I.; et al.; MAP kinase phosphatase-3 (MKP-3) is transcriptionally and post-translationally
up-regulated by hCG and modulates cAMP-induced p21 expression in MA-10
Leydig cells; Elsevier Ireland; Molecular And Cellular Endocrinology; 371; 1-2; 7-2013; 174-181
0303-7207
Autor
Mori Sequeiros Garcia, Mercedes
Gómez, Natalia
Gorostizaga, Alejandra Beatriz
Acquier, Andrea Beatriz
González Calvar, Silvia I.
Mendez, Carlos Fernando
Paz, Cristina del Valle
Resumen
Abstract Luteinizing hormone (LH) activates ERK1/2, MAP kinases (MAPK) necessary for its action on steroidogenesis and cell proliferation, and also induces MAPK phosphatase-1 (MKP-1), which rapidly dephosphorylates nuclear ERK1/2. MKP-3 is a cytoplasmic ERK-phosphatase up-regulated by proliferative stimuli. MKP-3 also dephosphorylates transcription factor FOXO1, promoting its transport to the nucleus. Here we analyzed MKP-3 expression in MA-10 Leydig cells and demonstrated that LH receptor (LHR) activation with human gonadotropin hormone (hCG) and an analog of its second messenger, 8Br-cAMP, up-regulates MKP-3 by transcriptional and post-translational mechanisms. It is known that FOXO1 drives the Expression of the cell cycle inhibitor p21. Since the activation of this transcription factor by MKP-3 has been reported, we assessed the effect of shRNA against MKP-3 on p21mRNA levels. 8Br-cAMP increased these levels (2-fold at 2 h) and MKP-3 down-regulation reduced this effect. Our work demonstrates that LH/hCG tightly up-regulates MKP-3 which in turn, dephosphorylates ERK1/2 and drives p21 expression. These events could contribute to counteract hormonal action on cell proliferation.