89 research outputs found
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Cytotoxic T lymphocytes can be generated against acetaldehyde-modified syngeneic cells
Acetaldehyde is a metabolic product of ethanol catabolism capable of forming protein adducts. These adducts have been found in situ and could account for the generation of anti-acetaldehyde antibodies found in various stages of alcoholic liver disease. Antibody production implicates participation of the cellular immune system. The existence of a cellular immune response poses the question of whether the body generates a cellular effector response against cells displaying these modified proteins. We have been able to show that murine splenic cells whose surface is acetaldehyde modified can generate cytotoxic T lymphocytes (CTL) in a syngeneic host when the stimulator cells carry the H-Y antigen and the responder population does not. This fact in conjunction with the finding that anti-class I antibody can block the anti-acetaldehyde CTL effector response supports the contention that the acetaldehyde-protein adducts are presented to the CTL in context with an intact class I MHC. This work supports the hypothesis that acetaldehyde-modified cells can generate a cellular immune response and may do so in pathologic states
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The generation of cytotoxic T lymphocytes against acetaldehyde-modified syngeneic cells
The Tumor Suppressor MIG6 Controls Mitotic Progression and the G2/M DNA Damage Checkpoint by Stabilizing the WEE1 Kinase
MIG6 is an important tumor suppressor that binds to and negatively regulates epidermal growth factor receptor (EGFR). Here, we report an EGFR-independent function for MIG6 as an integral component of the cell cycle machinery. We found that depletion of MIG6 causes accelerated entry into and delayed exit from mitosis. This is due to premature and prolonged activation of CDK1, a key regulator of mitotic progression at the G2/M and meta- and anaphase transitions. Furthermore, MIG6 is required for inhibition of CDK1 upon DNA damage and subsequent G2/M cell cycle arrest. Mechanistically, we found that MIG6 depletion results in reduced phosphorylation of CDK1 on the inhibitory WEE1-targeted tyrosine-15 residue. MIG6 interacts with WEE1 and promotes its stability by interfering with the recruitment of the βTrCP-SCF E3 ubiquitin ligase and consequent proteasomal degradation of WEE1. Our findings uncover a critical role of MIG6 in cell cycle progression that is likely to contribute to its potent tumor-suppressive properties
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