减毒的抗原呈递细胞（APC）等位基因通过内部翻译起始产生功能性蛋白质。
Attenuated APC alleles produce functional protein from internal translation initiation.
作者信息
Heppner Goss Kathleen, Trzepacz Chris, Tuohy Thérèse M F, Groden Joanna
机构信息
Department of Molecular Genetics, Biochemistry, and Microbiology, Howard Hughes Medical Institute, University of Cincinnati College of Medicine, 231 Albert Dabin Way, Cincinnati, OH 45267-0521, USA.
出版信息
Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8161-6. doi: 10.1073/pnas.112072199. Epub 2002 May 28.
Abstract
Some truncating mutations of the APC tumor suppressor gene are associated with an attenuated phenotype of familial adenomatous polyposis coli (AAPC). This work demonstrates that APC alleles with 5' mutations produce APC protein that down-regulates beta-catenin, inhibits beta-catenin/T cell factor-mediated transactivation, and induces cell-cycle arrest. Transfection studies demonstrate that cap-independent translation is initiated internally at an AUG at codon 184 of APC. Furthermore, APC coding sequence between AAPC mutations and AUG 184 permits internal ribosome entry in a bicistronic vector. These data suggest that AAPC alleles in vivo may produce functional APC by internal initiation and establish a functional correlation between 5' APC mutations and their associated clinical phenotype.
摘要
APC肿瘤抑制基因的一些截短突变与家族性腺瘤性息肉病（AAPC）的减弱表型相关。这项研究表明，具有5'端突变的APC等位基因产生的APC蛋白可下调β-连环蛋白，抑制β-连环蛋白/T细胞因子介导的反式激活，并诱导细胞周期停滞。转染研究表明，不依赖帽结构的翻译在APC第184密码子的AUG处内部起始。此外，AAPC突变与AUG 184之间的APC编码序列允许在双顺反子载体中进行内部核糖体进入。这些数据表明，体内的AAPC等位基因可能通过内部起始产生功能性APC，并在5'端APC突变与其相关临床表型之间建立功能相关性。
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