Università della Svizzera italiana

The MRE11 complex : a versatile toolkit for the repair of broken DNA

Reginato, Giordano ; Cejka, Petr

In: DNA repair, 2020, vol. 91–92, no. July–August, p. 13 p

When DNA breaks, the ends need to be stabilized and processed to facilitate subsequent repair, which can occur by either direct but error-prone end-joining with another broken DNA molecule or a more accurate homology-directed repair by the recombination machinery. At the same time, the presence of broken DNA triggers a signaling cascade that regulates the repair events and cellular progression...

Università della Svizzera italiana

SHP-2 in lymphocytes’ cytokine and inhibitory receptor signaling

Niogret, Charlène ; Birchmeier, Walter ; Guarda, Greta

In: Frontiers in immunology, 2019, vol. 10, no. 2468, p. 1-11

Somewhat counterintuitively, the tyrosine phosphatase SHP-2 (SH2 domain- containing protein tyrosine phosphatase-2) is crucial for the activation of extracellular signal-regulated kinase (ERK) downstream of various growth factor receptors, thereby exerting essential developmental functions. This phosphatase also deploys proto-oncogenic functions and specific inhibitors have recently been ...

Università della Svizzera italiana

Shp-2 is dispensable for establishing T cell exhaustion and for PD-1 signaling in vivo

Rota, Giorgia ; Niogret, Charlène ; Dang, Anh Thu ; Ramon Barros, Cristina ; Fonta, Nicolas Pierre ; Alfei, Francesca ; Morgado, Leonor ; Zehn, Dietmar ; Birchmeier, Walter ; Vivier, Eric ; Guarda, Greta

In: Cell reports, 2018, vol. 23, no. 1, p. 39-49

In chronic infection and cancer, T cells acquire a dysfunctional state characterized by the expression of inhibitory receptors. In vitro studies implicated the phosphatase Shp-2 downstream of these receptors, including PD-1. However, whether Shp-2 is responsible in vivo for such dysfunctional responses remains elusive. To address this, we generated T cell- specific Shp-2-deficient mice. These...