62 research outputs found
Negative feedback regulation of the ERK1/2 MAPK pathway
The extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) signalling pathway regulates many cellular functions, including proliferation, differentiation, and transformation. To reliably convert external stimuli into specific cellular responses and to adapt to environmental circumstances, the pathway must be integrated into the overall signalling activity of the cell. Multiple mechanisms have evolved to perform this role. In this review, we will focus on negative feedback mechanisms and examine how they shape ERK1/2 MAPK signalling. We will first discuss the extensive number of negative feedback loops targeting the different components of the ERK1/2 MAPK cascade, specifically the direct posttranslational modification of pathway components by downstream protein kinases and the induction of de novo gene synthesis of specific pathway inhibitors. We will then evaluate how negative feedback modulates the spatiotemporal signalling dynamics of the ERK1/2 pathway regarding signalling amplitude and duration as well as subcellular localisation. Aberrant ERK1/2 activation results in deregulated proliferation and malignant transformation in model systems and is commonly observed in human tumours. Inhibition of the ERK1/2 pathway thus represents an attractive target for the treatment of malignant tumours with increased ERK1/2 activity. We will, therefore, discuss the effect of ERK1/2 MAPK feedback regulation on cancer treatment and how it contributes to reduced clinical efficacy of therapeutic agents and the development of drug resistance
Site-specific AT-cluster insertions in the mitochondrial 15S rRNA gene of the yeast S. cerevisiae.
By comparing the mitochondrial 15S rRNA sequences of four wildtype yeast strains together with their respective secondary structures, with those of the 16S-like ribosomal RNA from other organisms we detected two optional and two invariant AT-clusters. The origin of these clusters is discussed with respect to their roles as possible mobile elements
A controversy concerning the structure of the mitochondrial genome of a yeast petite mutant: resolution by sequence analysis
At least two nuclear-encoded factors are involved together with a mitochondrial factor (MR1) in spontaneous mitochondrial frameshift-suppression of the yeast S. cerevisiae
Mitochondrial mutations restricting spontaneous translational frameshift suppression in the yeast Saccharomyces cerevisiae
Transcripts of yeast Mitochondrial DNA: processing of a split gene transcript and expression ofRNA species during adaptation and differentiation processes
A mitochondrial frameshift suppressor maps in the tRNASer-var1 region of the mitochondrial genome of the yeast S. cerevisiae
A mitochondrial frameshift-suppressor (+) of the yeast S. cerevisiae maps in the mitochondrial 15S rRNA locus
RNA splicing in yeast mitochondria: DNA sequence analysis of mit − mutants deficient in the excision of introns aI1 and aI2 of the gene for subunit I of cytochrome c oxidase
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