Proteolytic activation of SREBPs during adipocyte differentiation
Proteolytic activation of SREBPs during adipocyte differentiation
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DOI：
10.1006/bbrc.2001.4915
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发表时间：
2001-05-25
影响因子：
3.1
通讯作者：
Sato, R
中科院分区：
文献类型：
--
作者：
Inoue, J;Kumagai, H;Sato, R
固醇调节元件结合蛋白（SREBP-1）是固醇调节元件结合蛋白（SREBP）家族的成员，是脂肪细胞分化的关键调节因子。SREBP-1基因的表达在脂肪细胞分化过程中被诱导，但合成的SREBP-1前体形式的蛋白水解活化尚未得到很好的分析。SREBP的蛋白水解加工在固醇负载的培养细胞中受到严重抑制。在这里，我们报告说，剪接异构体，SREBP-1a，主要是在3 T3-L1前脂肪细胞和脂肪细胞中表达，并且SREBP-1蛋白的核活性形式在脂肪细胞分化中增加。我们进一步表明，核SREBP-2蛋白的量也增加，尽管SREBP-2 mRNA没有增加，表明SREBP的蛋白水解裂解在脂质负载的脂肪细胞中被诱导。北方印迹分析显示，参与SREBP蛋白水解加工的SHEEP裂解激活蛋白（SCAP）、位点1蛋白酶（S1 P）和位点2蛋白酶（S2 P）的mRNA水平在脂肪形成中相对不受影响，这些结果表明，SREBP-2似乎与SREBP-1一样促进脂肪细胞分化，并且SREBP的蛋白水解活化可能由作为脂肪细胞的蛋白酶抑制剂诱导。在脂质负载的脂肪细胞中尚未确定的机制（C）2001学术出版社。
A member of sterol regulatory element-binding protein (SREBP) family, SREBP-1, is a key regulator of adipocyte differentiation. Expression of the SREBP-1 gene is induced during adipocyte differentiation, but proteolytic activation of the synthesized precursor form of SREBP-1 has not been well analyzed. The proteolytic processing of SREBPs is severely suppressed in sterol loaded culture cells. Here we report that a splicing isoform, SREBP-1a, is predominantly expressed in 3T3-L1 preadipocytes and adipocytes, and that the nuclear active form of SREBP-1 protein increases in adipocyte differentiation. We further show that the amount of nuclear SREBP-2 protein also increases despite no increase in SREBP-2 mRNA, suggesting that proteolytic cleavage of SREBPs is induced in lipid loaded adipocytes. Northern blot analyses reveal that mRNA levels for SHEEP cleavage-activating protein (SCAP), Site-1 protease (S1P), and Site-2 protease (S2P), which participate in the proteolytic processing of SREBPs, are relatively unaffected in adipogenesis, These results demonstrate that SREBP-2 appears to promote adipocyte differentiation as well as SREBP-1 and that the proteolytic activation of SREBPs may be induced by an as-yet unidentified mechanism in lipid loaded adipocytes (C) 2001 Academic Press.