Lim D S, Kirsch D G, Canman C E, Ahn J H, Ziv Y, Newman L S, Darnell R B, Shiloh Y, Kastan M B
Oncology Center, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):10146-51. doi: 10.1073/pnas.95.17.10146.
Inherited mutations in the ATM gene lead to a complex clinical phenotype characterized by neuronal degeneration, oculocutaneous telangiectasias, immune dysfunction, and cancer predisposition. Using the yeast two-hybrid system, we demonstrate that ataxia telangiectasia mutated (ATM) binds to beta-adaptin, one of the components of the AP-2 adaptor complex, which is involved in clathrin-mediated endocytosis of receptors. The interaction between ATM and beta-adaptin was confirmed in vitro, and coimmunoprecipitation and colocalization studies show that the proteins also associate in vivo. ATM also interacts in vitro with beta-NAP, a neuronal-specific beta-adaptin homolog that was identified as an autoantigen in a patient with cerebellar degeneration. Our data describing the association of ATM with beta-adaptin in vesicles indicate that ATM may play a role in intracellular vesicle and/or protein transport mechanisms.
ATM基因的遗传性突变会导致一种复杂的临床表型,其特征为神经元变性、眼皮肤毛细血管扩张、免疫功能障碍和癌症易感性。利用酵母双杂交系统,我们证明了共济失调毛细血管扩张突变基因(ATM)与β-衔接蛋白结合,β-衔接蛋白是AP-2衔接复合体的组成成分之一,参与网格蛋白介导的受体胞吞作用。ATM与β-衔接蛋白之间的相互作用在体外得到了证实,免疫共沉淀和共定位研究表明这两种蛋白在体内也相互关联。ATM在体外还与β-NAP相互作用,β-NAP是一种神经元特异性β-衔接蛋白同源物,在一名小脑变性患者中被鉴定为自身抗原。我们关于ATM与囊泡中β-衔接蛋白关联的数据表明,ATM可能在细胞内囊泡和/或蛋白质转运机制中发挥作用。