Negative Regulators in Cancer Immunology and Immunotherapy

Author(s):  
Wolfgang Zimmermann ◽  
Robert Kammerer
2004 ◽  
Vol 171 (4S) ◽  
pp. 46-46
Author(s):  
Carlos R. Estrada ◽  
Theodora Danciu ◽  
Maximilian Stehr ◽  
Joseph Khoury ◽  
Keith R. Solomon ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Antonio P. A. Ferreira ◽  
Alessandra Casamento ◽  
Sara Carrillo Roas ◽  
Els F. Halff ◽  
James Panambalana ◽  
...  

AbstractEndocytosis mediates the cellular uptake of micronutrients and cell surface proteins. Fast Endophilin-mediated endocytosis, FEME, is not constitutively active but triggered upon receptor activation. High levels of growth factors induce spontaneous FEME, which can be suppressed upon serum starvation. This suggested a role for protein kinases in this growth factor receptor-mediated regulation. Using chemical and genetic inhibition, we find that Cdk5 and GSK3β are negative regulators of FEME. They antagonize the binding of Endophilin to Dynamin-1 and to CRMP4, a Plexin A1 adaptor. This control is required for proper axon elongation, branching and growth cone formation in hippocampal neurons. The kinases also block the recruitment of Dynein onto FEME carriers by Bin1. As GSK3β binds to Endophilin, it imposes a local regulation of FEME. Thus, Cdk5 and GSK3β are key regulators of FEME, licensing cells for rapid uptake by the pathway only when their activity is low.


2009 ◽  
Vol 191 (9) ◽  
pp. 3050-3058 ◽  
Author(s):  
Sadanobu Abe ◽  
Ayako Yasumura ◽  
Teruo Tanaka

ABSTRACT Expression of the gene for the extracellular alkaline protease (aprE) of Bacillus subtilis is subject to regulation by many positive and negative regulators. We have found that aprE expression was increased by disruption of the glutamine synthetase gene glnA. The increase in aprE expression was attributed to a decreased in expression of scoC, which encodes a negative regulator of aprE expression. The glnA effect on scoC expression was abolished by further disruption of tnrA, indicating that aprE expression is under global regulation through TnrA. In the scoC background, however, aprE expression was decreased by glnA deletion, and it was shown that the decrease was due to a defect in positive regulation by DegU. Among the genes that affect aprE expression through DegU, the expression of degR, encoding a protein that stabilizes phosphorylated DegU, was inhibited by glnA deletion. It was further shown that the decrease in degR expression by glnA deletion was caused by inhibition of the expression of sigD, encoding the σD factor, which is required for degR expression. In accordance with these findings, the expression levels of aprE-lacZ in glnA scoC degR and scoC degR strains were identical. These results led us to conclude that glnA deletion brings about two effects on aprE expression, i.e., a positive effect through inhibition of scoC expression and a negative effect through inhibition of degR expression, with the former predominating over the latter.


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