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Ornithine decarboxylase
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| Identifiers | |
| Symbol | ODC1 |
| Entrez | 4953 |
| HUGO | 8109 |
| OMIM | 165640 |
| PDB | 7odc |
| RefSeq | NM_002539 |
| UniProt | P11926 |
| Other data | |
| EC number | 4.1.1.17 |
| Locus | Chr. 2 p25 |
The enzyme ornithine decarboxylase (ODC) is a homodimer of 461 amino acids (in humans, at least).
Contents |
Reaction
It catalyzes the decarboxylation of ornithine producing, as a result, diamine putrescine:
This is the first step and the rate limiting step in humans for the production of polyamines, compounds required for cell division.
Clinical significance
ODC gene expression is induced by a large number of biological stimuli including seizure activity in the brain.[1]. Inactivation of ODC by difluoromethylornithine (eflornithine) is used to treat cancer, sleeping sickness and facial hair growth in postmenopausal females.
ODC is also an enzyme indispensable to parasites like trypanosoma, giardia and plasmodium. A fact abused by the drug eflornithine.
Ubiquitin-independent proteasomal degradation
ODC is the most well-characterized cellular protein subject to ubiquitin-independent proteasomal degradation. Although most proteins must first be tagged with multiple ubiquitin molecules before they are bound and degraded by the proteasome, ODC degradation is instead mediated by several recognition sites on the protein and its accessory factor antizyme 1. The ODC degradation process is regulated in a negative feedback loop by its reaction products.[2]
Until a report by Sheaff et al. (2000)[3], which demonstrated that the cyclin-dependent kinase (Cdk) inhibitor p21Cip1 is also degraded by the proteasome in a ubiquitin-independent manner, ODC was only clear example of ubiquitin-independent proteasomal degradation.[4]
External links
References
- ^ Herberg LJ, Rose IC, de Belleroche JS, Mintz M (1992). "Ornithine decarboxylase induction and polyamine synthesis in the kindling of seizures: the effect of alpha-difluoromethylornithine". Epilepsy Res. 11 (1): 3–7. doi:. PMID 1563337.
- ^ Zhang M, Pickart CM, Coffino P. (2003). Determinants of proteasome recognition of ornithine decarboxylase, a ubiquitin-independent substrate. EMBO J 22 (7): 1488 - 1496.
- ^ Sheaff RJ, Singer JD, Swanger J, Smitherman M, Roberts JM, Clurman BE. (2000). Proteasomal Turnover of p21Cip1 Does Not Require p21Cip1 Ubiquitination. Mol. Cell 5: 403 - 410.
- ^ Verma R, Deshaies RJ. (2000). A Proteasome Howdunit: The Case of the Missing Signal. Cell 101: 341 - 344.
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