Uyttendaele H, Marazzi G, Wu G, Yan Q, Sassoon D, Kitajewski J
Department of Pathology in the Center of Reproductive Sciences, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Development. 1996 Jul;122(7):2251-9. doi: 10.1242/dev.122.7.2251.
The int-3 oncogene was identified as a frequent target in Mouse Mammary Tumor Virus (MMTV)-induced mammary carcinomas and encodes the intracellular domain of a novel mouse Notch gene. To investigate the role of the int-3 proto-oncogene in mouse development and carcinogenesis, we isolated cDNA clones corresponding to the entire coding potential of the int-3 proto-oncogene. We propose to name this gene Notch4 and reserve the int-3 nomenclature for references to the oncogenic form. The deduced amino acid sequence of Notch4 contains conserved motifs found in Notch proteins; however Notch4 has fewer epidermal growth factor (EGF)-like repeats and a shorter intracellular domain than other mouse Notch homologues. Comparison of the coding potential of the int-3 gene to that of Notch4 suggests that loss of the extracellular domain of Notch4 leads to constitutive activation of this murine Notch protein. In situ hybridization revealed that Notch4 transcripts are primarily restricted to endothelial cells in embryonic and adult life. Truncated Notch4 transcripts were detected in post-meiotic male germ cells. The distinct Notch4 protein features and its restricted expression pattern suggests a specific role for Notch4 during development of vertebrate endothelium.
int-3癌基因被确定为小鼠乳腺肿瘤病毒（MMTV）诱导的乳腺癌中的常见靶点，并编码一种新型小鼠Notch基因的细胞内结构域。为了研究int-3原癌基因在小鼠发育和致癌过程中的作用，我们分离了与int-3原癌基因的整个编码潜能相对应的cDNA克隆。我们建议将该基因命名为Notch4，并保留int-3的命名法用于指代致癌形式。Notch4推导的氨基酸序列包含在Notch蛋白中发现的保守基序；然而，与其他小鼠Notch同源物相比，Notch4具有较少的表皮生长因子（EGF）样重复序列和较短的细胞内结构域。int-3基因与Notch4编码潜能的比较表明，Notch4细胞外结构域的缺失导致该小鼠Notch蛋白的组成性激活。原位杂交显示，Notch4转录本主要局限于胚胎期和成年期的内皮细胞。在减数分裂后的雄性生殖细胞中检测到截短的Notch4转录本。Notch4独特的蛋白特征及其受限的表达模式表明Notch4在脊椎动物内皮发育过程中具有特定作用。
