THE BLI-4 LOCUS OF CAENORHABDITIS-ELEGANS ENCODES STRUCTURALLY DISTINCT KEX2/SUBTILISIN-LIKE ENDOPROTEASES ESSENTIAL FOR EARLY DEVELOPMENT AND ADULT MORPHOLOGY
THE BLI-4 LOCUS OF CAENORHABDITIS-ELEGANS ENCODES STRUCTURALLY DISTINCT KEX2/SUBTILISIN-LIKE ENDOPROTEASES ESSENTIAL FOR EARLY DEVELOPMENT AND ADULT MORPHOLOGY
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DOI：
10.1101/gad.9.8.956
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发表时间：
1995-04-15
影响因子：
10.5
通讯作者：
ROSE, AM
中科院分区：
文献类型：
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作者：
THACKER, C;PETERS, K;ROSE, AM
许多分泌性蛋白质是通过在成对的碱性残基处切割而从无活性的前蛋白上切下的。最近的研究已经确定了几种丝氨酸内切蛋白酶，催化这种裂解在酵母和后生动物的分泌途径。这些酶属于前蛋白转化酶的kex 2/枯草杆菌蛋白酶样家族。在本文中，我们描述了从秀丽隐杆线虫，这是以前的致死突变体的遗传分析是必不可少的这种生物体的正常发展的BLI-4基因的分子特征。cDNA和基因组克隆的测序显示，bli-4编码与前蛋白转化酶的kex 2/枯草杆菌蛋白酶样家族相关的基因产物。对bli-4 cDNA的分析预测了四种蛋白产物，我们将其命名为水泡酶A、B、C和D。这些蛋白质产物共享一个共同的氨基末端，但在羧基末端不同，并且最有可能由选择性剪接的转录物产生。我们已经确定了三个bli-4等位基因（h199，h1010和q508）的分子病变，导致胚胎发生后期发育停滞。在每种情况下，分子病变都在所有BLI-4同种型共有的外显子内。bli-4的原始定义等位基因e937是完全可行的，但表现出成年表皮起泡。对该等位基因的分子分析揭示了去除外显子13的缺失，这是水泡酶A所特有的。在besterred突变体中没有检测到对应于外显子13的RNA转录物。这些发现表明，水泡酶A是成人表皮正常功能所必需的。bli-4基因是一个复杂的基因座，突变株和RNA转录物的表征证明了这一点。此外，我们的数据表明，功能冗余可能存在于各种BLI-4亚型之间。
Many secreted proteins are excised from inactive proproteins by cleavage at pairs of basic residues. Recent studies have identified several serine endoproteases that catalyze this cleavage in the secretory pathways of yeast and metazoans. These enzymes belong to the kex2/subtilisin-like family of proprotein convertases. In this paper we describe the molecular characterization of the bli-4 gene from Caenorhabditis elegans, which was shown previously by genetic analysis of lethal mutants to be essential for the normal development of this organism. Sequencing of cDNA and genomic clones has revealed that bli-4 encodes gene products related to the kex2/subtilisin-like family of proprotein convertases. Analysis of bli-4 cDNAs has predicted four protein products, which we have designated blisterases A,B,C, and D. These protein products share a common amino terminus, but differ at the carboxyl termini, and are most likely produced from alternatively spliced transcripts. We have determined the molecular lesions for three bli-4 alleles (h199, h1010, and q508) that result in developmental arrest during late embryogenesis. In each case, the molecular lesions are within exons common to all of the BLI-4 isoforms. The original defining allele of bli-4, e937, is completely viable yet exhibits blistering of the adult cuticle. Molecular analysis of this allele revealed a deletion that removes exon 13, which is unique to blisterase A. No RNA transcript corresponding to exon 13 is detectable in the blistered mutants. These findings suggest that blisterase A is required for the normal function of the adult cuticle. The bli-4 gene is a complex locus as evidenced by the characterization of mutant strains and RNA transcripts. Furthermore, our data show that functional redundancy may exist among the various BLI-4 isoforms.