Regulation of the SCF(Met30p) Ubiquitin Ligase Complex

Lsu Health Sciences Center -Shreveport, Shreveport LA

Investigators

Abstract

An important means of regulating a protein's activity is to regulate its abundance. A family of multi-protein complexes, called SCF complexes, target protein substrates for degradation. The substrate recognition component of an SCF complex is called the F-box protein. Different F-box proteins are present in a cell, and form distinct SCF complexes that will recognize different protein substrates. SCF complexes are evolutionarily conserved, being found in a wide range of organisms, and play key roles in diverse biological pathways, such as cell division and metabolism. Although SCF complexes play a crucial role in biology, little is known about how their activity is regulated. F-box proteins are substrates for degradation, suggesting that their abundance regulates the activity of their respective SCF complex. Indeed, the abundance of the F-box protein Met30p appears to regulate the activity of the SCFMet30p complex. This research project is directed towards understanding how the abundance of Met30p is controlled . The SCFMet30p complex regulates the process of sulfur uptake and metabolism. Sulfur is found in many molecules essential for life, such as the amino acid methionine. Fungi such as yeast have the ability to take up elemental sulfur and, through a series of metabolic steps, convert it to methionine. Through this process of sulfur fixation, methionine and other sulfur-containing molecules can be synthesized. The SCFMet30p complex negatively regulates the process of sulfur fixation. In the presence of methionine, the SCFMet30p complex inhibits sulfur uptake and metabolism. Preliminary data support the hypothesis that methionine availability plays a role in regulating Met30p abundance in yeast . An immediate goal of this project is to monitor the abundance of Met30p, SCFMet30p substrates and the activity of genes involved in sulfur metabolism as cells make the transition from an environment containing methionine to an environment lacking methionine. This work will test the hypothesis that SCFMet30p complex activity is regulated by Met30p abundance, which is in turn regulated by methionine availability. Furthermore, this work will describe the process regulating sulfur uptake and methionine synthesis. Additional aims of this research project are to: i) identify genes that are involved in regulating Met30p abundance and ii) identify amino acid residues within Met30p that target it for degradation. This work will describe how changes in environmental conditions are sensed and permit the modulation of Met30p abundance in order to regulate SCFMet30p complex activity. SCF complexes, present in fungi and in other multi-cellular organisms, coordinate cellular responses to a diverse range of environmental signals. The abundance of the F-box proteins associated with these SCF complexes appear to be regulated. This research program will improve the understanding of a process that may be fundamental to all cells.