2012年5月31日 · In this study we demonstrate that Cbl-b does not regulate PI3K but rather inhibits the Ub ligase activity of Nedd4, which targets Pten for K63-linked polyubiquitination, thus suppressing inactivation of Pten. Cbl-b may exert its effect on Pten by impeding the binding of Pten to Nedd4, which is independent of its E3 Ub ligase activity (Figure S5 ...

Importantly Cbl-b is the only member of the Cbl family which has been documented to be crucial for T cell tolerance. In this brief review, we summarize the major work that we and others have carried out investigating Cbl-b in T cell tolerance and autoimmunity, proallergic T cell development, and cancer immunity.

Suppression of Pten inactivation in T cells by Cbl-b is achieved by impeding the association of Pten with Nedd4, which targets Pten K13 for K63-linked polyubiquitination. Consistent with this finding, introducing Nedd4 defi-/ ciency into Cbl-b mice abrogates hyper-T cell responses caused by the loss of Cbl-b.

2020年12月9日 · Nucleus–cytoplasm shuttling of PTEN is regulated by ubiquitylation, SUMOylation and phosphorylation, and nuclear PTEN has been proposed to exhibit tumor-suppressive functions. Here we show that...

Casitas B lymphoma-b (Cbl-b), a RING finger E3 ubiquitin ligase, has been identified as a critical regulator of adaptive immune responses. Cbl-b is essential for establishing the threshold for T cell activation and regulating peripheral T cell tolerance through various mechanisms.

PTEN was constitutively associated with c-Cbl, protecting it from degradation. EphB1 stimulation triggered ∼50% serine-threonine PTEN dephosphorylation and PTEN-Cbl complex disruption, a process requiring PTEN protein phosphatase activity.

Here, we investigated the role of the E3 ubiquitin ligase casitas B-lineage lymphoma-b (Cbl-b) in establishing CD8+ T-cell resistance to Treg-mediated suppression to enhance antitumor immunity....

2012年5月31日 · Suppression of Pten inactivation in T cells by Cbl-b is achieved by impeding the association of Pten with Nedd4, which targets Pten K13 for K63-linked polyubiquitination. Consistent with this finding, introducing Nedd4 deficiency into Cbl-b (-/-) mice abrogates hyper-T cell responses caused by the loss of Cbl-b.

In this study we demonstrate that Cbl-b does not regulate PI3K but rather inhibits the Ub ligase activity of Nedd4, which targets Pten for K63-linked polyubiquitination, thus suppressing inactivation of Pten. Cbl-b may exert its effect on Pten by impeding the binding of Pten to Nedd4, which is independent of its E3 Ub ligase activity . This ...

Casitas B-lineage lymphoma proto-oncogene-b (Cbl-b), a RING finger E3 ubiquitin-protein ligase, has been demonstrated to play a crucial role in establishing the threshold for T-cell activation and controlling peripheral T-cell tolerance via multiple mechanisms.