Endothelial cells from patients with mutations exhibit increased proliferation and an inability to form vascular networks (9).
Variable dependence on S1 cleavage also extends to T-ALL-associated NRR mutations, as common class 1 mutations display variable decrements in ligand-independent activation when introduced into furin-resistant receptors, whereas a class 2 mutation exhibits increased signaling activity.
Notably, melanomas that have the V600E BRAF mutation exhibit increased HIF-1α expression.
G2019S pathogenic mutation exhibits increased kinase activity and is phosphorylated to wild-type (WT) levels at Ser910/935/955/973.
In contrast, Atm knock-in heterozygous mice harbouring an in-frame deletion corresponding to the human mutation exhibit increased susceptibility to a wide variety of tumours [ 14].
We found that sperm obtained that were heterozygously or homozygously deleted of the Pol B gene exhibited increased mutation frequencies compared to wild-type sperm.
The Rub1 protein is also related to fungal transmigration into the CNS; mutant possessing a null mutation in the putative Rub1 gene exhibited increased transmigration into the brain [ 13].
In models of endotoxemia, mice heterozygous for mutations in antithrombin III and protein C exhibited increased tissue fibrin deposition and mortality compared with wild-type controls, presumably due to reduced levels of antithrombin III and active protein C [ 27].
The lethal H5N1 strains with a point mutation, D92E, or a deletion of residues 80-84 in the NS1 protein, exhibited increased virulence, cytokine resistance or both [27].
Cells lacking the mitochondrial division component Fis1p, however, were not resistant to these agents, and even exhibited increased sensitivity to CHX, demonstrating that not all mutations permitting mtDNA maintenance by fzo1 ∆ aac2 ∆ cells lead to PDR activation.
