Reactome | Regulation of ornithine decarboxylase (ODC)

Regulation of ornithine decarboxylase (ODC)

Stable Identifier

R-HSA-350562

Type

Pathway

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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Regulation of ornithine decarboxylase (ODC)

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Polyamines increase the production of antizyme (AZ). The carboxy-terminal half of antizyme interacts with ODC, generating an inactive AZ:ODC heterodimer complex. A carboxy-terminal domain of ODC is exposed only within the heterodimer, and is the target for subsequent degradation. A domain within the amino-terminal portion of antizyme provides a function needed for efficient degradation of ODC by the proteasome.
The proteasome cycle starts with the processing of AZ:ODC, sequestering ODC and then degrading it to peptides but releasing AZ. AZ participates in additional rounds of binding and degradation. Antizyme-mediated inhibition and destruction of ODC reduces synthesis of polyamines. Additionally, antizyme also inhibits polyamine transport into the cell. Antizyme production is reduced, completing the regulatory circuit (Coffino 2001; Kahana et al. 2005; Murakami et al. 2000; Pegg 2006).

Literature References

PubMed ID	Title	Journal	Year
16205122	Mechanisms of protein degradation: an odyssey with ODC Kahana, C, Asher, G, Shaul, Y	Cell Cycle	2005
11265248	Regulation of cellular polyamines by antizyme Coffino, P	Nat Rev Mol Cell Biol	2001
10623564	Degradation of ornithine decarboxylase by the 26S proteasome Murakami, Y, Matsufuji, S, Hayashi, S, Tanahashi, N, Tanaka, K	Biochem Biophys Res Commun	2000
16459331	Regulation of ornithine decarboxylase Pegg, AE	J Biol Chem	2006