CHARACTERIZATION OF THE ATAXIA-TELANGIECTASIA GENE PRODUCT

A-T是一种常染色体隐性遗传疾病，其特征是眼皮肤 毛细血管扩张和进行性神经运动功能障碍，细胞和 体液免疫缺陷、对电离辐射过敏， 增加白血病和淋巴瘤的易感性。350 kD蛋白 产物类似于磷脂酰肌醇-3 '激酶样分子， 作为丝氨酸/苏氨酸激酶。我们已经产生了多克隆抗体， 这让我们将ATM蛋白定义为 主要是核蛋白，可能作为传感器， 基因组DNA中的双链断裂。最近的结果涉及 解剖负责核靶向的序列基序， 鉴定该蛋白在p53介导的细胞凋亡和细胞周期中的作用 这表明Bax和p21的诱导可能存在差异， 在ATM空背景下。ATM对p53介导的 Bax诱导证实了细胞凋亡的激活。

A-T is an autosomal recessive disorder characterized by oculocutaneous telangiectasias and progressive neuromotor dysfunction, cellular and humoral immune deficiencies, hypersensitivity to ionizing radiation and increased predisposition to leukemias and lymphomas. The 350 kD protein product resembles a phosphatidylinositol-3' kinase-like molecule but acts as a serine/threonine kinase.We have generated polyclonal antibodies against the ATM protein that led us to define the ATM protein as a predominantly nuclear protein that likely functions as a sensor for double-strand breaks in genomic DNA. More recent results involves dissecting the sequence motif responsible for nuclear targeting and in identifying the protein's role in p53-mediated apoptosis and cell cycle which indicates that there can be differential induction of Bax and p21 in the Atm null background. Atm apparently has no effect on p53-mediated activation of apoptosis as evidenced by Bax induction.