ATP- and antizyme-dependent endoproteolysis of ornithine decarboxylase to oligopeptides by the 26 S proteasome

Tokunaga, Fuminori; Goto, Takahiro; Koide, Tie; Murakami, Yasuko; Hayashi, Shin Ichi; Tamura, Tomohiro; Tanaka, K.; Ichihara, Akira

doi:10.1016/s0021-9258(17)32448-1

Cited by 54 publications

(2 citation statements)

References 22 publications

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“…This suggests the requirement of a specific proteolytic process, such as that involving the 26 S proteasome, rather than a non-specific protease sensitivity. Published reports [32], and ongoing studies in our lab, indicate that antizyme is not readily degraded in rabbit reticulocyte lysate, an in itro system that normally promotes degradation of other proteins that are substrates for the 26 S proteasome. It may be that the initiation of antizyme degradation requires an additional, unidentified, factor, the same way that rapid ODC degradation requires the presence of antizyme.…”

Section: Discussionmentioning

confidence: 96%

Osmotic stress induces variation in cellular levels of ornithine decarboxylase-antizyme

Mitchell

Judd

Leyser

et al. 1998

Biochemical Journal

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The polyamines, and especially putrescine, play an integral role in the physiological response of cells to varying extracellular osmotic conditions. Ornithine decarboxylase (ODC) synthesis and stability, as well as the activity of the polyamine transporter, had all been reported to be very sensitive to media osmolarity in different cells and tissues, yet the mechanism of this complex, co-ordinated response was not known. In this study we have determined that all these aspects of osmotic-shock response may be mediated by the common regulatory protein, ODC-antizyme. HTC cells were induced for antizyme and then exposed to media of reduced osmotic strength. Both antizyme activity and protein decreased rapidly, under these conditions, to new steady-state levels that depended upon the degree of reduction in media tonicity. This antizyme reduction was found to be due to a rapid increase in antizyme degradation, with a half-life decrease from 75 min down to 45 min occurring immediately upon exchanging media. In complementary experiments, increased media tonicity induced elevated antizyme levels and stability. The sensitivity of antizyme turnover to osmotic conditions was also observed in DH23b cells, which contain elevated levels of more stable antizyme. Interestingly, the two main antizyme proteins, AZ-1 and AZ-2 (presumably products from the first and second translational start sites), differed in their responses to these changing osmotic conditions. Just as feedback regulation of antizyme synthesis provides an effective mechanism for maintaining stable polyamine levels, these studies suggest that alteration in the rate of antizyme degradation may be the mechanism whereby cells adjust steady-state polyamine levels in response to stimulation or stress.

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Section: Discussionmentioning

confidence: 96%

Osmotic stress induces variation in cellular levels of ornithine decarboxylase-antizyme

Mitchell

Judd

Leyser

et al. 1998

Biochemical Journal

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“…ODC is a pivotal protein molecule that participates in the biosynthesis of various polyamines. AZ, which stands for "antienzyme for ornithine decarboxylase", is a regulatory protein of ODC and was initially verified as an important enzyme in polyamine biosynthesis (27,28). The direct combination of ODC and AZ results in a change in the three-dimensional structure of ODC that exposes the proteasome-binding site in its carboxyl terminus (29,30).…”

Section: Introductionmentioning

confidence: 99%

Ubiquitin‐independent, Proteasome‐mediated targeted degradation of KRAS in pancreatic adenocarcinoma cells using an engineered ornithine decarboxylase/antizyme system

Huang

et al. 2018

IUBMB Life

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The oncogene KRAS not only promotes the tumorigenesis of pancreatic cancers but also is required for the malignant progression and metastasis of these cancers. Many methods have been explored to influence the malignant biological behavior of these cancers by targeting mutant KRAS. The ornithine decarboxylase/antizyme (ODC/AZ) system is another protein degradation pathway that exists in nature. The formation of an ODC and protein substrate complex through direct combination can promote its degradation by the 26S proteasome without ubiquitination, and this process can be catalyzed by AZ. In this study, we designed and reconstructed a chimeric fusion protein (named RC‐ODC). The engineered fusion protein RC‐ODC was confirmed to interact with the mutant KRAS oncoprotein in a co‐immunoprecipitation assay, and the introduction of both RC‐ODC and AZ resulted in degradation of the exogenous and endogenous mutant KRAS oncoprotein at the post‐translational level independent of ubiquitination in vitro. Along with a decreased KRAS level, suppression of PANC‐1 cell proliferation was detected in vitro and in vivo, and meanwhile downregulation of phosphorylated extracellular signal‐regulated kinase 1/2 (ERK1/2) was also observed. Targeted degradation of the KRAS oncoprotein through the ODC/AZ pathway at the post‐translational level may reflect a more effective future therapeutic strategy for pancreatic cancer patients. © 2018 The Authors. IUBMB Life published by Wiley Periodicals,Inc. on behalf of International Union of Biochemistry and Molecular Biology, 71(1):57–65, 2019

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Crystallization of a mammalian ornithine decarboxylase

et al. 1996

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ATP- and antizyme-dependent endoproteolysis of ornithine decarboxylase to oligopeptides by the 26 S proteasome

Cited by 54 publications

References 22 publications

Osmotic stress induces variation in cellular levels of ornithine decarboxylase-antizyme

Osmotic stress induces variation in cellular levels of ornithine decarboxylase-antizyme

Ubiquitin‐independent, Proteasome‐mediated targeted degradation of KRAS in pancreatic adenocarcinoma cells using an engineered ornithine decarboxylase/antizyme system

Crystallization of a mammalian ornithine decarboxylase

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