Unknown

Dataset Information

0

Regulation of all members of the antizyme family by antizyme inhibitor.


ABSTRACT: ODC (ornithine decarboxylase) is the rate-limiting enzyme in polyamine biosynthesis. Polyamines are essential for cellular growth and differentiation but enhanced ODC activity is associated with cell transformation. Post-translationally, ODC is negatively regulated through members of the antizyme family. Antizymes inhibit ODC activity, promote ODC degradation through the 26 S proteasome and regulate polyamine transport. Besides the ubiquitously expressed antizymes 1 and 2, there is the tissue-specific antizyme 3 and an yet uncharacterized antizyme 4. Antizyme 1 has been shown to be negatively regulated through the AZI (antizyme inhibitor) that binds antizyme 1 with higher affinity compared with ODC. In the present study, we show by yeast two- and three-hybrid protein-protein interaction studies that AZI interacts with all members of the antizyme family and is capable of disrupting the interaction between each antizyme and ODC. In a yeast-based ODC complementation assay, we show that human ODC is able to complement fully the function of the yeast homologue of ODC. Co-expression of antizymes resulted in ODC inhibition and cessation of yeast growth. The antizyme-induced growth inhibition could be reversed by addition of putrescine or by the co-expression of AZI. The protein interactions could be confirmed by immunoprecipitation of the human ODC-antizyme 2-AZI complexes. In summary, we conclude that human AZI is capable of acting as a general inhibitor for all members of the antizyme family and that the previously not yet characterized antizyme 4 is capable of binding ODC and inhibiting its enzymic activity similar to the other members of the antizyme family.

SUBMITTER: Mangold U 

PROVIDER: S-EPMC1134669 | biostudies-other | 2005 Jan

REPOSITORIES: biostudies-other

Similar Datasets

| S-EPMC4551939 | biostudies-literature
| S-EPMC3196680 | biostudies-literature
| S-EPMC3135638 | biostudies-literature
| S-EPMC2785365 | biostudies-literature
| S-EPMC3084279 | biostudies-literature
| S-EPMC3170320 | biostudies-literature
| S-EPMC7846877 | biostudies-literature
| S-EPMC3114525 | biostudies-literature
| S-EPMC4066113 | biostudies-literature
| S-EPMC4568681 | biostudies-literature