81 research outputs found
Phosphorylation of Kif26b Promotes Its Polyubiquitination and Subsequent Proteasomal Degradation during Kidney Development
Kif26b, a member of the kinesin superfamily proteins (KIFs), is essential for kidney development. Kif26b expression is restricted to the metanephric mesenchyme, and its transcription is regulated by a zinc finger transcriptional regulator Sall1. However, the mechanism(s) by which Kif26b protein is regulated remain unknown. Here, we demonstrate phosphorylation and subsequent polyubiquitination of Kif26b in the developing kidney. We find that Kif26b interacts with an E3 ubiquitin ligase, neural precursor cell expressed developmentally down-regulated protein 4 (Nedd4) in developing kidney. Phosphorylation of Kif26b at Thr-1859 and Ser-1962 by the cyclin-dependent kinases (CDKs) enhances the interaction of Kif26b with Nedd4. Nedd4 polyubiquitinates Kif26b and thereby promotes degradation of Kif26b via the ubiquitin-proteasome pathway. Furthermore, Kif26b lacks ATPase activity but does associate with microtubules. Nocodazole treatment not only disrupts the localization of Kif26b to microtubules but also promotes phosphorylation and polyubiquitination of Kif26b. These results suggest that the function of Kif26b is microtubule-based and that Kif26b degradation in the metanephric mesenchyme via the ubiquitin-proteasome pathway may be important for proper kidney development
Rheological profile across the NE Japan interplate megathrust in the source region of the 2011 Mw9.0 Tohoku-oki earthquake
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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
Characterization and phylogenetic distribution of a chloroplast DNA rearrangement in theBerberidaceae
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