Discovery of a spermatogenesis stage-specific ornithine decarboxylase antizyme: Antizyme 3
Discovery of a spermatogenesis stage-specific ornithine decarboxylase antizyme: Antizyme 3
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DOI：
10.1073/pnas.070055897
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发表时间：
2000-04-25
影响因子：
11.1
通讯作者：
Atkins, JF
中科院分区：
文献类型：
--
作者：
Ivanov, IP;Rohrwasser, A;Atkins, JF
以往的研究表明，小鼠产生过量的鸟氨酸脱羧酶的重要性，多胺稳态正常哺乳动物精子发生。本研究介绍了一个可能的关键球员在维持适当的多胺稳态精子发生过程中。抗酶3是哺乳动物鸟氨酸脱羧酶抗酶的一种。与先前描述的对应物抗酶1和2一样，它抑制催化腐胺合成的鸟氨酸脱羧酶。早期的研究表明，抗酶1和2的编码序列位于两个不同的、部分重叠的阅读框架中。核糖体翻译第一个阅读框，就在该框的终止密码子之前，它们转移到第二个阅读框以合成跨框产物。这种移码的效率取决于多胺的浓度，形成一个自动调节回路。抗酶3 cDNA具有相同的阅读框排列和潜在的移位位点，与其进化上遥远的抗酶1和3对应物具有明确的同源性，尽管有限。与广泛表达于全身的抗酶1和2相反，抗酶3的转录仅限于睾丸生殖细胞。表达在精子发生早期开始，在精子细胞晚期结束。本文就抗酶3在精子发生过程中的表达及其意义进行了讨论。
Previous studies with mice overproducing ornithine decarboxylase have demonstrated the importance of polyamine homeostasis for normal mammalian spermatogenesis. The present study introduces a likely key player in the maintenance of proper polyamine homeostasis during spermatogenesis. Antizyme 3 is a paralog of mammalian ornithine decarboxylase antizymes. Like its previously described counterparts, antizymes 1 and 2, it inhibits ornithine decarboxylase, which catalyzes the synthesis of putrescine. Earlier work has shown that the coding sequences for antizymes 1 and 2 are in two different, partially overlapping reading frames. Ribosomes translate the first reading frame, and just before the stop codon for that frame, they shift to the second reading frame to synthesize a trans-frame product. The efficiency of this frameshifting depends on polyamine concentration, creating an autoregulatory circuit. Antizyme 3 cDNA has the same arrangement of reading frames and a potential shift site with definite, although limited, homology to its evolutionarily distant antizyme 1 and 3 counterparts. In contrast to antizymes 1 and 2, which are widely expressed throughout the body, antizyme 3 transcription is restricted to testis germ cells. Expression starts early in spermiogenesis and finishes in the late spermatid phase. The potential significance of antizyme 3 expression during spermatogenesis is discussed in this paper.