Saltar al contenido
Merck

Regulation of Bone Morphogenetic Protein Signaling by ADP-ribosylation.

The Journal of biological chemistry (2016-04-30)
Yukihide Watanabe, Panagiotis Papoutsoglou, Varun Maturi, Yutaro Tsubakihara, Michael O Hottiger, Carl-Henrik Heldin, Aristidis Moustakas
RESUMEN

We previously established a mechanism of negative regulation of transforming growth factor β signaling mediated by the nuclear ADP-ribosylating enzyme poly-(ADP-ribose) polymerase 1 (PARP1) and the deribosylating enzyme poly-(ADP-ribose) glycohydrolase (PARG), which dynamically regulate ADP-ribosylation of Smad3 and Smad4, two central signaling proteins of the pathway. Here we demonstrate that the bone morphogenetic protein (BMP) pathway can also be regulated by the opposing actions of PARP1 and PARG. PARG positively contributes to BMP signaling and forms physical complexes with Smad5 and Smad4. The positive role PARG plays during BMP signaling can be neutralized by PARP1, as demonstrated by experiments where PARG and PARP1 are simultaneously silenced. In contrast to PARG, ectopic expression of PARP1 suppresses BMP signaling, whereas silencing of endogenous PARP1 enhances signaling and BMP-induced differentiation. The two major Smad proteins of the BMP pathway, Smad1 and Smad5, interact with PARP1 and can be ADP-ribosylated in vitro, whereas PARG causes deribosylation. The overall outcome of this mode of regulation of BMP signal transduction provides a fine-tuning mechanism based on the two major enzymes that control cellular ADP-ribosylation.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Sigma-Aldrich
ANTI-FLAG® M2 monoclonal antibody produced in mouse, 1 mg/mL, clone M2, affinity isolated antibody, buffered aqueous solution (50% glycerol, 10 mM sodium phosphate, and 150 mM NaCl, pH 7.4)
Número de referencia del producto (SKU)
Tamaño de envase
Disponibilidad
Precio
Cantidad
Sigma-Aldrich
Monoclonal ANTI-FLAG® M5 antibody produced in mouse, clone M5, purified immunoglobulin, buffered aqueous solution
Número de referencia del producto (SKU)
Tamaño de envase
Disponibilidad
Precio
Cantidad
Sigma-Aldrich
Anti-PARG Antibody, clone D8B10, clone D8B10, from mouse
Número de referencia del producto (SKU)
Tamaño de envase
Disponibilidad
Precio
Cantidad