Id-related genes encoding helix-loop-helix proteins are required for G1 progression and are repressed in senescent human fibroblasts.
Id-related genes encoding helix-loop-helix proteins are required for G1 progression and are repressed in senescent human fibroblasts.
复制标题
DOI：
10.1016/s0021-9258(17)42146-6
复制
发表时间：
1994-01
期刊：
影响因子：
--
通讯作者：
E. Hara;T. Yamaguchi;H. Nojima;T. Ide;J. Campisi;Hiroto Okayama;K. Oda
中科院分区：
文献类型：
--
作者：
E. Hara;T. Yamaguchi;H. Nojima;T. Ide;J. Campisi;Hiroto Okayama;K. Oda
从TIG-3人二倍体成纤维细胞(HDF)的pcD2表达文库中分离到3个编码ID相关的螺旋-环-螺旋(HLH)蛋白的全长cDNA克隆。在这些cDNA(ID-1H、ID-1H‘和ID-2H)中，有两个(ID-1H和ID-1H’)似乎是通过选择性RNA剪接获得的。ID-1H和ID-2H似乎分别是小鼠ID-1和ID-2的人类同源物，分别编码154和135个氨基酸。在静止的早期传代的HDF中几乎检测不到ID-1H和ID-2H的mRNAs；血清协同诱导了这两个mRNAs，在G1期的早期和晚期出现了两个表达高峰。与ID-1H和ID-2H基因互补的反义寡聚物可阻止早期传代的HDF进入细胞周期的S期。用反义ID-1H寡聚体处理血清刺激的早期传代细胞，可完全消除ID-1H。在衰老细胞中，血清诱导ID-1H和ID-2H的mRNAs，但在早期传代细胞和衰老细胞中诱导的c-myc表达水平相似。这些ID基因的表达水平在不同的永生人类细胞系中有所不同。这两个基因在VA4-SV40转化的肺成纤维细胞和EJ-1膀胱癌细胞中高表达，而在SV40-TSA转化的TIG-3细胞的SVts8细胞中低水平表达。SVts8细胞可能获得一些ID蛋白多余的功能。HT1080纤维肉瘤细胞表达ID-1H基因，但不表达ID-2H基因，提示这些ID基因可能取代了多余的功能。
Three complete cDNA clones encoding Id-related helix-loop-helix (HLH) proteins lacking a basic region were isolated from a pcD2 cDNA expression library prepared from TIG-3 human diploid fibroblasts (HDF). Of these cDNAs (Id-1H, Id-1H', and Id-2H), two (Id-1H and Id-1H') appeared to be derived by alternative RNA splicing. Id-1H and Id-2H seem to be human homologues of mouse Id-1 and Id-2, respectively, and have potential to encode 154 and 135 amino acid proteins. The Id-1H and Id-2H mRNAs were barely detectable in quiescent early passage HDF; serum coordinately induced both mRNAs, with two peaks of expression, in early and late in G1. Antisense oligomers complementary to Id-1H and Id-2H mRNA prevented early passage HDF from entering the S phase of the cell cycle. The treatment of serum-stimulated early passage cells with the antisense Id-1H oligomer completely abolished Id-1H. In senescent cells, serum barely induced the Id-1H and Id-2H mRNAs, although the levels of c-myc expression induced were similar in early passage and senescent cells. The expression levels of these Id genes vary among immortal human cell lines. Both genes were overexpressed in VA4 SV40-transformed lung fibroblasts and EJ-1 bladder carcinoma cells, while these genes were expressed at a very low level in SVts8 cells derived from SV40 tsA-transformed TIG-3 cells. SVts8 cells may acquire some function redundant to Id proteins. HT1080 fibrosarcoma cells expressed the Id-1H gene but not the Id-2H gene, suggesting these Id genes may subserve redundant functions.