Search results for "Protein Phosphatase 2C"

Wip1 inhibition leads to severe pro-inflammatory phenotype in skin in response to chemical irritation

2016

Autoantibodies in Spondyloarthritis, Focusing on Anti-CD74 Antibodies

2019

Spondyloarthritis (SpA) is an inflammatory rheumatic disease with diverse clinical presentation. The diagnosis of SpA remains a big challenge in daily clinical practice because of the limitation in specific biomarkers of SpA, more biomarkers are still needed for SpA diagnosis and disease activity monitoring. In the past, SpA was considered predominantly as auto-inflammatory disease vs. autoimmune disease. However, in recent years several researches demonstrated a broad autoantibody response in SpA patients. Study also indicated that mice lack of ZAP70 in T cell develop SpA featured inflammation. These studies indicated the autoimmune features of SpA and gave rise to the potential use of aut…

Role of Gadd45a in Wip1-dependent regulation of intestinal tumorigenesis.

2012

Conversion of intestinal stem cells into tumor-initiating cells is an early step in Apc(Min)-induced polyposis. Wild-type p53-induced phosphatase 1 (Wip1)-dependent activation of a DNA damage response and p53 has a permanent role in suppression of stem cell conversion, and deletion of Wip1 lowers the tumor burden in Apc(Min) mice. Here we show that cyclin-dependent kinase inhibitor 2a, checkpoint kinase 2, and growth arrest and DNA damage gene 45a (Gadd45a) exert critical functions in the tumor-resistant phenotype of Wip1-deficient mice. We further identified Gadd45a as a haploinsufficient gene in the regulation of Wip1-dependent tumor resistance in mice. Gadd45a appears to function through…

Wip1 phosphatase: between p53 and MAPK kinases pathways.

2016

IF 5.008; International audience; Cells undergoing oncogenic transformation frequently inactivate tumor suppressor pathways that could prevent their uncontrolled growth. Among those pathways p53 and p38MAPK pathways play a critical role in regulation of cell cycle, senescence and cell death in response to activation of oncogenes, stress and DNA damage. Consequently, these two pathways are important in determining the sensitivity of tumor cells to anti-cancer treatment. Wild type p53-induced phosphatase, Wip1, is involved in governance of both pathways. Recently, strategies directed to manipulation with Wip1 activity proposed to advance current day anticancer treatment and novel chemical com…

Wee1 inhibition potentiates Wip1-dependent p53-negative tumor cell death during chemotherapy

2016

AbstractInactivation of p53 found in more than half of human cancers is often associated with increased tumor resistance to anti-cancer therapy. We have previously shown that overexpression of the phosphatase Wip1 in p53-negative tumors sensitizes them to chemotherapeutic agents, while protecting normal tissues from the side effects of anti-cancer treatment. In this study, we decided to search for kinases that prevent Wip1-mediated sensitization of cancer cells, thereby interfering with efficacy of genotoxic anti-cancer drugs. To this end, we performed a flow cytometry-based screening in order to identify kinases that regulated the levels of γH2AX, which were used as readout. Another criter…