Munemitsu S, Souza B, Müller O, Albert I, Rubinfeld B, Polakis P
Onyx Pharmaceuticals, Richmond, California 94806.
Cancer Res. 1994 Jul 15;54(14):3676-81.
Defects in the APC gene occur frequently in patients with familial adenomatous polyposis coli and are associated with the progression of sporadic tumors of the colon and stomach. We examined the subcellular location of adenomatous polyposis coli (APC) protein resulting from transient expression of full length and partial APC complementary DNAs in epithelial cells. Immunofluorescent detection revealed an association of APC with cytoplasmic microtubules. Expression of partial complementary DNA constructs indicated that the carboxy-terminal region of the APC protein, typically deleted in cancers, is essential for this association. The same APC polypeptides that associated with microtubules in vivo also dramatically promoted their assembly in vitro. These results suggest that wild-type APC protein binds to and affects the assembly of microtubules, whereas the mutants identified in tumors have lost this activity.
APC基因缺陷在家族性腺瘤性息肉病患者中频繁出现，并与结肠和胃部散发性肿瘤的进展相关。我们检测了全长和部分APC互补DNA在上皮细胞中瞬时表达所产生的腺瘤性息肉病（APC）蛋白的亚细胞定位。免疫荧光检测显示APC与细胞质微管相关。部分互补DNA构建体的表达表明，APC蛋白的羧基末端区域（通常在癌症中缺失）对于这种关联至关重要。在体内与微管相关的相同APC多肽在体外也显著促进了它们的组装。这些结果表明，野生型APC蛋白结合并影响微管的组装，而在肿瘤中鉴定出的突变体已丧失这种活性。
