The change of antizyme inhibitor expression and its possible role during mammalian cell cycle

Murakami, Yasuko; Suzuki, Junichiro; Samejima, Keijiro; Kikuchi, Kenjiro; Hascilowicz, Tomasz; Murai, Noriyuki; Matsufuji, Senya; Oka, Takami

doi:10.1016/j.yexcr.2009.04.024

Cited by 20 publications

(22 citation statements)

References 49 publications

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“…The synthesis of ODC antizyme is stimulated by polyamines through a frameshifting mechanism, possibly through a direct interaction of polyamines with antizyme mRNA or via alternative mechanisms, including an interaction of polyamines with ODC antizyme at the translational level. The story has recently become even more complex with the finding that antizyme itself is regulated by an ODC-related protein termed antizyme inhibitor, lacking enzymatic activity [7].…”

Section: Polyamine Synthesis and Functionsmentioning

confidence: 99%

The Polyamine Pathway as a Potential Target for Vascular Diseases: Focus on Restenosis

Forte¹,

Hellstrand²,

Nilsson³

et al. 2011

CVP

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Section: Polyamine Synthesis and Functionsmentioning

confidence: 99%

The Polyamine Pathway as a Potential Target for Vascular Diseases: Focus on Restenosis

Forte¹,

Hellstrand²,

Nilsson³

et al. 2011

CVP

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“…AZI is an inactive homolog of ODC which has lost decarboxylation activity due to mutation of critical residues in the active site [24],[25],[26],[46],[62]. However, they are important in mammals as they are responsible for antizyme down regulations, thus regulate the ODC activity in cell system [21].…”

Section: Resultsmentioning

confidence: 99%

“…Previously, it has been reported that AZI is homologous to ODC and the major residues involved in catalytic activity of ODC are conserved in AZI [24]. However, AZI does not possess enzymatic activity due to changes in the sequence that lead to protein inability to bind cofactor PLP along with the failure in decarboxylation activity [24],[25],[26].…”

Section: Introductionmentioning

confidence: 99%

Structural Insight into DFMO Resistant Ornithine Decarboxylase from Entamoeba histolytica: An Inkling to Adaptive Evolution

et al. 2013

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BackgroundPolyamine biosynthetic pathway is a validated therapeutic target for large number of infectious diseases including cancer, giardiasis and African sleeping sickness, etc. α-Difluoromethylornithine (DFMO), a potent drug used for the treatment of African sleeping sickness is an irreversible inhibitor of ornithine decarboxylase (ODC), the first rate limiting enzyme of polyamine biosynthesis. The enzyme ODC of E. histolytica (EhODC) has been reported to exhibit resistance towards DFMO.Methodology/Principal FindingThe basis for insensitivity towards DFMO was investigated by structural analysis of EhODC and conformational modifications at the active site. Here, we report cloning, purification and crystal structure determination of C-terminal truncated Entamoeba histolytica ornithine decarboxylase (EhODCΔ15). Structure was determined by molecular replacement method and refined to 2.8 Å resolution. The orthorhombic crystal exhibits P212121 symmetry with unit cell parameters a = 76.66, b = 119.28, c = 179.28 Å. Functional as well as evolutionary relations of EhODC with other ODC homologs were predicted on the basis of sequence analysis, phylogeny and structure.Conclusions/SignificanceWe determined the tetrameric crystal structure of EhODCΔ15, which exists as a dimer in solution. Insensitivity towards DFMO is due to substitution of key substrate binding residues in active site pocket. Additionally, a few more substitutions similar to antizyme inhibitor (AZI), a non-functional homologue of ODCs, were identified in the active site. Here, we establish the fact that EhODC sequence has conserved PLP binding residues; in contrast few substrate binding residues are mutated similar to AZI. Further sequence analysis and structural studies revealed that EhODC may represent as an evolutionary bridge between active decarboxylase and inactive AZI.

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“…Azin1 has been shown to act as a major regulator of Odc activity and polyamine levels during cell growth and transformation. However, studies have also shown that polyamines can inhibit Azin1 via a negative feedback loop (Ivanov et al, 2008;Murakami et al, 2009;Ivanov et al, 2010). A further study suggested that this inhibition mainly occurs at the translational level through a short upstream open reading frame (ORF) with a non-AUG start codon (Murakami et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Molecular cloning and mRNA expression analysis of antizyme inhibitor 1 in the ovarian follicles of the Sichuan white goose

Jiang

Kang

et al. 2015

Gene

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The change of antizyme inhibitor expression and its possible role during mammalian cell cycle

Cited by 20 publications

References 49 publications

The Polyamine Pathway as a Potential Target for Vascular Diseases: Focus on Restenosis

The Polyamine Pathway as a Potential Target for Vascular Diseases: Focus on Restenosis

Structural Insight into DFMO Resistant Ornithine Decarboxylase from Entamoeba histolytica: An Inkling to Adaptive Evolution

Molecular cloning and mRNA expression analysis of antizyme inhibitor 1 in the ovarian follicles of the Sichuan white goose

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