Gangisetty Omkaram, Lauffart Brenda, Sondarva Gautam V, Chelsea Diane M, Still Ivan H
Department of Cancer Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
Oncogene. 2004 Apr 1;23(14):2559-63. doi: 10.1038/sj.onc.1207424.
Dysregulation of the human transforming acidic coiled coil (TACC) genes is thought to be important in the development of multiple myeloma, breast and gastric cancer. However, even though these proteins have been implicated in the control of cell growth and differentiation, the mechanism by which they function still remains to be clarified. Using the yeast two-hybrid assay, we have now identified the histone acetyltransferase (HAT) hGCN5L2 as a TACC2-binding protein. GST pull-down analysis subsequently confirmed that all human TACC family members can bind in vitro to hGCN5L2. The authenticity of these interactions was validated by coimmunoprecipitation assays within the human embryonic kidney cell line HEK293, which identified the TACC2s isoform as a component consistently bound to several different members of HAT family. This raises the possibility that aberrant expression of one or more TACC proteins may affect gene regulation through their interaction with components of chromatin remodeling complexes, thus contributing to tumorigenesis.
人类转化酸性卷曲螺旋（TACC）基因的失调被认为在多发性骨髓瘤、乳腺癌和胃癌的发展中起重要作用。然而，尽管这些蛋白质与细胞生长和分化的控制有关，但其发挥作用的机制仍有待阐明。利用酵母双杂交试验，我们现已鉴定出组蛋白乙酰转移酶（HAT）hGCN5L2是一种TACC2结合蛋白。随后的GST下拉分析证实，所有人类TACC家族成员均可在体外与hGCN5L2结合。这些相互作用的真实性通过人胚肾细胞系HEK293中的免疫共沉淀试验得到验证，该试验确定TACC2的异构体是与HAT家族的几个不同成员持续结合的一个成分。这增加了一种可能性，即一种或多种TACC蛋白的异常表达可能通过它们与染色质重塑复合物成分的相互作用影响基因调控，从而促进肿瘤发生。
