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The emerging regulatory potential of SCFMet30 -mediated polyubiquitination and proteolysis of the Met4 transcriptional activator.

Chandrasekaran S, Skowyra D - Cell Div (2008)

Bottom Line: We revisit this model in light of the growing evidence that SCFMet30 can also activate Met4.The notion that Met4 can be inhibited or activated depending on the sulfur metabolite context is not new, but for the first time both aspects have been linked to SCFMet30, creating an interesting regulatory paradigm in which polyubiquitination and proteolysis of a single transcriptional activator can play different roles depending on context.We discuss the emerging molecular basis and the implications of this new regulatory phenomenon.

View Article: PubMed Central - HTML - PubMed

Affiliation: Edward A, Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St, Louis, MO, 63104, USA. skowyrad@slu.edu.

ABSTRACT
The yeast SCFMet30 ubiquitin ligase plays a critical role in cell division by regulating the Met4 transcriptional activator of genes that control the uptake and assimilation of sulfur into methionine and S-adenosyl-methionine. The initial view on how SCFMet30 performs its function has been driven by the assumption that SCFMet30 acts exclusively as Met4 inhibitor when high levels of methionine drive an accumulation of cysteine. We revisit this model in light of the growing evidence that SCFMet30 can also activate Met4. The notion that Met4 can be inhibited or activated depending on the sulfur metabolite context is not new, but for the first time both aspects have been linked to SCFMet30, creating an interesting regulatory paradigm in which polyubiquitination and proteolysis of a single transcriptional activator can play different roles depending on context. We discuss the emerging molecular basis and the implications of this new regulatory phenomenon.

No MeSH data available.


Related in: MedlinePlus

Roadmap highlighting the relationship between the SCFMet30-Met4 interplay and the regulatory schemes involved in sulfur assimilation, oxidative stress and cell division. The model emphasizes the notion that the SCFMet30 ubiquitin ligase activates the Met4 transcriptional activator in a manner linked to cell division and dependent on low levels of methionine, allowing expression of the MET and SAM genes encoding the enzymes assimilating sulfur into methionine and S-adenosyl-methionine, respectively (green). In a negative feedback response driven by methionine accumulation, with the biosynthesis of S-adenosyl-methionine and cysteine necessary in this regulatory context, Met4 activation by SCFMet30 is blocked, leading to Met4 inhibition (purple). Navy blue indicates steps involved in oxidative stress response induced by cadmium (Cd2+). Note that Sam1 and Sam2 enzymes are necessary for all three types of responses, emphasizing the special regulatory role of S-adenosyl-methionine biosynthesis. Methionine, S-adenosyl-methionine and cysteine are necessary for the biosynthesis and modification of proteins, lipids and nucleotides during growth (turquoise). See text for details.
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Figure 1: Roadmap highlighting the relationship between the SCFMet30-Met4 interplay and the regulatory schemes involved in sulfur assimilation, oxidative stress and cell division. The model emphasizes the notion that the SCFMet30 ubiquitin ligase activates the Met4 transcriptional activator in a manner linked to cell division and dependent on low levels of methionine, allowing expression of the MET and SAM genes encoding the enzymes assimilating sulfur into methionine and S-adenosyl-methionine, respectively (green). In a negative feedback response driven by methionine accumulation, with the biosynthesis of S-adenosyl-methionine and cysteine necessary in this regulatory context, Met4 activation by SCFMet30 is blocked, leading to Met4 inhibition (purple). Navy blue indicates steps involved in oxidative stress response induced by cadmium (Cd2+). Note that Sam1 and Sam2 enzymes are necessary for all three types of responses, emphasizing the special regulatory role of S-adenosyl-methionine biosynthesis. Methionine, S-adenosyl-methionine and cysteine are necessary for the biosynthesis and modification of proteins, lipids and nucleotides during growth (turquoise). See text for details.

Mentions: In free-living single-celled organisms like yeast, metabolic pathways are exquisitely tuned to the availability of nutrients in the environment. The likelihood of sudden changes in availability of metabolites has led such organisms to acquire complex and dynamic feedback mechanisms that link nutrient availability to the control of biosynthetic pathways and to cell proliferation. The sulfur assimilation pathway is emerging as one of the most interesting examples of such a system, with the Met4 transcriptional activator involved in the uptake and assimilation of sulfur into the amino acids methionine and S-adenosyl-methionine (Fig. 1, green) regulated not only by the metabolites, but also by cell division and oxidative stress-mediated responses.


The emerging regulatory potential of SCFMet30 -mediated polyubiquitination and proteolysis of the Met4 transcriptional activator.

Chandrasekaran S, Skowyra D - Cell Div (2008)

Roadmap highlighting the relationship between the SCFMet30-Met4 interplay and the regulatory schemes involved in sulfur assimilation, oxidative stress and cell division. The model emphasizes the notion that the SCFMet30 ubiquitin ligase activates the Met4 transcriptional activator in a manner linked to cell division and dependent on low levels of methionine, allowing expression of the MET and SAM genes encoding the enzymes assimilating sulfur into methionine and S-adenosyl-methionine, respectively (green). In a negative feedback response driven by methionine accumulation, with the biosynthesis of S-adenosyl-methionine and cysteine necessary in this regulatory context, Met4 activation by SCFMet30 is blocked, leading to Met4 inhibition (purple). Navy blue indicates steps involved in oxidative stress response induced by cadmium (Cd2+). Note that Sam1 and Sam2 enzymes are necessary for all three types of responses, emphasizing the special regulatory role of S-adenosyl-methionine biosynthesis. Methionine, S-adenosyl-methionine and cysteine are necessary for the biosynthesis and modification of proteins, lipids and nucleotides during growth (turquoise). See text for details.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2526995&req=5

Figure 1: Roadmap highlighting the relationship between the SCFMet30-Met4 interplay and the regulatory schemes involved in sulfur assimilation, oxidative stress and cell division. The model emphasizes the notion that the SCFMet30 ubiquitin ligase activates the Met4 transcriptional activator in a manner linked to cell division and dependent on low levels of methionine, allowing expression of the MET and SAM genes encoding the enzymes assimilating sulfur into methionine and S-adenosyl-methionine, respectively (green). In a negative feedback response driven by methionine accumulation, with the biosynthesis of S-adenosyl-methionine and cysteine necessary in this regulatory context, Met4 activation by SCFMet30 is blocked, leading to Met4 inhibition (purple). Navy blue indicates steps involved in oxidative stress response induced by cadmium (Cd2+). Note that Sam1 and Sam2 enzymes are necessary for all three types of responses, emphasizing the special regulatory role of S-adenosyl-methionine biosynthesis. Methionine, S-adenosyl-methionine and cysteine are necessary for the biosynthesis and modification of proteins, lipids and nucleotides during growth (turquoise). See text for details.
Mentions: In free-living single-celled organisms like yeast, metabolic pathways are exquisitely tuned to the availability of nutrients in the environment. The likelihood of sudden changes in availability of metabolites has led such organisms to acquire complex and dynamic feedback mechanisms that link nutrient availability to the control of biosynthetic pathways and to cell proliferation. The sulfur assimilation pathway is emerging as one of the most interesting examples of such a system, with the Met4 transcriptional activator involved in the uptake and assimilation of sulfur into the amino acids methionine and S-adenosyl-methionine (Fig. 1, green) regulated not only by the metabolites, but also by cell division and oxidative stress-mediated responses.

Bottom Line: We revisit this model in light of the growing evidence that SCFMet30 can also activate Met4.The notion that Met4 can be inhibited or activated depending on the sulfur metabolite context is not new, but for the first time both aspects have been linked to SCFMet30, creating an interesting regulatory paradigm in which polyubiquitination and proteolysis of a single transcriptional activator can play different roles depending on context.We discuss the emerging molecular basis and the implications of this new regulatory phenomenon.

View Article: PubMed Central - HTML - PubMed

Affiliation: Edward A, Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St, Louis, MO, 63104, USA. skowyrad@slu.edu.

ABSTRACT
The yeast SCFMet30 ubiquitin ligase plays a critical role in cell division by regulating the Met4 transcriptional activator of genes that control the uptake and assimilation of sulfur into methionine and S-adenosyl-methionine. The initial view on how SCFMet30 performs its function has been driven by the assumption that SCFMet30 acts exclusively as Met4 inhibitor when high levels of methionine drive an accumulation of cysteine. We revisit this model in light of the growing evidence that SCFMet30 can also activate Met4. The notion that Met4 can be inhibited or activated depending on the sulfur metabolite context is not new, but for the first time both aspects have been linked to SCFMet30, creating an interesting regulatory paradigm in which polyubiquitination and proteolysis of a single transcriptional activator can play different roles depending on context. We discuss the emerging molecular basis and the implications of this new regulatory phenomenon.

No MeSH data available.


Related in: MedlinePlus