Open AccessDNA damage-induced phosphatase Wip1 in regulation of hematopoiesis, immune system and inflammation
Author(s) -
Burhan Uyanik,
Bogdan B. Grigorash,
Anastasia R. Goloudina,
Oleg N. Demidov
Publication year - 2017
Publication title -
cell death discovery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.556
H-Index - 28
ISSN - 2058-7716
DOI - 10.1038/cddiscovery.2017.18
Subject(s) - inflammation , immune system , haematopoiesis , microbiology and biotechnology , dna , dna damage , phosphatase , chemistry , biology , immunology , biochemistry , phosphorylation , stem cell
PP2C serine–threonine phosphatase, Wip1, is an important regulator of stress response. Wip1 controls a number of critical cellular functions: proliferation, cell cycle arrest, senescence and programmed cell death, apoptosis or autophagy. Ppm1d , the gene encoding Wip1 phosphatase, is expressed in hematopoietic progenitors, stem cells, neutrophils, macrophages B and T lymphocytes in bone marrow and peripheral blood. The Wip1−/− mice display immunodeficiency, abnormal lymphoid histopathology in thymus and spleen, defects in B- and T-cell differentiation, as well as susceptibility to viral infection. At the same time, Wip1 knockout mice exhibit pro-inflammatory phenotype in skin and intestine in the model of inflammatory bowel disease (IBD) with elevated levels of inflammation-promoting cytokines TNF- α , IL-6, IL-12, IL-17. Several Wip1 downstream targets can mediate Wip1 effects on hematopoietic system including, p53, ATM, p38MAPK kinase, NF k B, mTOR. Here, we summarized the current knowledge on the role of Wip1 in the differentiation of various hematopoietic lineages and how Wip1 deficiency affects the functions of immune cells.