Senescence marker protein-30 (SMP30): Structure and biological function

Senescence marker protein-30 (SMP30): Structure and biological function
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DOI:
10.1006/bbrc.1998.9841
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发表时间:
1999-01-08
影响因子:
3.1
通讯作者:
Fujita, T
Fujita, T
中科院分区:
生物学4区
文献类型:
--
作者:
Fujita, T

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我们先前鉴定的衰老标记蛋白-30(SMP 30)以其在衰老大鼠肝脏中的雄激素非依赖性减少而闻名。肝细胞和肾小管上皮细胞在整个组织成熟过程和成年期的胞质溶胶中表达大量的SMP 30,但此后其水平降低。在克隆编码大鼠、小鼠和人的SMP 30的cDNA后,我们发现SMP 30的氨基酸序列在这些物种中具有很好的保守性和显著的同源性。然而,这种在这些高等动物中非常保守的基因并没有出现在酵母中。我们还测定了小鼠基因组中SMP 30的基因组结构和5'侧翼区。与此同时,SMP 30被证明与称为regucalcin(RC)的Ca 2+结合蛋白相同。为了了解这种蛋白质的功能,我们用人SMP 30 cDNA转染Hep G2细胞,以便这些细胞稳定表达大量的SMP 30。结果表明,SMP 30通过增强质膜中的Ca 2+泵活性来调节Ca 2+稳态。因此,SMP 30似乎在肝脏和肾脏的高度分化的功能中发挥关键作用,并对Ca 2+稳态产生重大影响。如果是这样的话,随着年龄的增长,SMP 30的下调将极大地归因于这些器官的相关退化,正如SMP 30的结构,表达和功能的简要概述所示。(C)北京:科学出版社.
Senescence marker protein-30 (SMP30), which we previously identified, is notable for its androgen-independent decrease in the livers of aging rats. Hepatocytes and renal tubular epithelia express large amounts of SMP30 in their cytosol throughout the tissue-maturing process and adulthood, but its level decreases thereafter. Upon cloning cDNAs that encode SMP30 in rats, mice, and humans, we found that the amino acid sequence of SMP30 is well conserved with remarkable homology among these species. However, this gene, which is so strongly conserved in these higher animals, does not appear in yeast. We also determined the genome organization and 5' flanking region of SMP30 in mouse genome. In the meantime, SMP30 turned out be identical to a Ca2+-binding protein called regucalcin (RC). To learn how this protein functions, we transfected Hep G2 cells with human SMP30 cDNA so that these cells stably express large amounts of SMP30. The results suggest that SMP30 regulates Ca2+ homeostasis by enhancing Ca2+-pumping activity in the plasma membranes. Thus, SMP30 seems to play a critical role in the highly differentiated functions of the liver and kidney and to exert a major impact on Ca2+ homeostasis. If so, down-regulation of SMP30 with aging would attribute greatly to the related deterioration of these organs, as indicated in this brief overview of the structure, expression, and function Of SMP30. (C) 1999 Academic Press.