SARPs: A family of secreted apoptosis-related proteins
SARPs: A family of secreted apoptosis-related proteins
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DOI：
10.1073/pnas.94.25.13636
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发表时间：
1997-12-09
影响因子：
11.1
通讯作者：
Umansky, SR
中科院分区：
文献类型：
--
作者：
Melkonyan, HS;Chang, WC;Umansky, SR
与处于指数生长期的细胞相比，静止的小鼠胚胎C3H/10T1/2细胞对不同的促凋亡刺激具有更强的抵抗力，而指数生长的10T1/2细胞对核糖核酸或蛋白质合成的抑制剂具有抵抗力，而静止的细胞在这些处理下死亡，来自静止的10T1/2细胞的条件培养液具有抗凋亡活性，这表明存在作为凋亡程序抑制因子的蛋白质(S)。利用差异显示技术，我鉴定并克隆了一个rDNA，命名为Sarp1(分泌型凋亡相关蛋白)，它在静止的BUR中表达，而不是在指数级生长的101/2细胞中表达。与Sarp1的杂交研究揭示了两个额外的家族成员，克隆和测序表明，Sarp2和Sarp3的序列与Sarp1的序列同源性分别为38%和40%。稳定转染人乳腺腺癌细胞MCF7或感染转染腺病毒SARP1的MCF7细胞对不同促凋亡刺激的敏感性增强。SARP家族成员的表达具有组织特异性，SARP编码的分泌型蛋白具有与卷曲蛋白CRD同源的半胱氨酸富含结构域(CRD)，但缺乏可能的跨膜片段，SARP的表达改变了细胞内β-连环素的水平，表明SARPs干扰了WNT-卷曲蛋白的信号通路。
Quiescent mouse embryonic C3H/10T1/2 cells are more resistant to different proapoptotic stimuli than are these cells in the exponential phase of growth, However the exponentially growing 10T1/2 cells are resistant to inhibitors of RNA or protein synthesis, whereas quiescent cells die upon these treatments, Conditioned medium from quiescent 10T1/2 cells possesses anti-apoptotic activity, suggesting the presence of protein(s) that function as an inhibitor of the apoptotic program. Using differential display technique, me identified and cloned a rDNA designated sarp1 (secreted apoptosis-related protein) that is expressed in quiescent bur not in exponentially growing 101/2 cells. Hybridization studies with sarp1 revealed two additiional family members, Cloning and sequencing of sarp2 and sarp3 revealed 38% and 40% sequence identity to sarp1, respectively. Human breast adenocarcinoma MCF7 cells stably transfected with sarp1 or infected with SARP1-expressing adenovirus became more resistant, whereas cells transfected with sarp2 displayed increased sensitivity to different proapoptotic stimuli. Expression of sarp family members is tissue specific, sarp mRNAs encode secreted proteins that possess a cysteine-rich domain (CRD) homologous to the CRD of frizzled proteins but lack putative membrane-spanning segments, Expression of SARPs modifies the intracellular levels of beta-catenin, suggesting that SARPs interfere with the Wnt-frizzled proteins signaling pathway.