Department of Vertebrate Genomics, Max-Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
Nat Commun. 2013;4:1531. doi: 10.1038/ncomms2517.
Centrosome morphology and number are frequently deregulated in cancer cells. Here, to identify factors that are functionally relevant for centrosome abnormalities in cancer cells, we established a protein-interaction network around 23 centrosomal and cell-cycle regulatory proteins, selecting the interacting proteins that are deregulated in cancer for further studies. One of these components, LGALS3BP, is a centriole- and basal body-associated protein with a dual role, triggering centrosome hypertrophy when overexpressed and causing accumulation of centriolar substructures when downregulated. The cancer cell line SK-BR-3 that overexpresses LGALS3BP exhibits hypertrophic centrosomes, whereas in seminoma tissues with low expression of LGALS3BP, supernumerary centriole-like structures are present. Centrosome hypertrophy is reversed by depleting LGALS3BP in cells endogenously overexpressing this protein, supporting a direct role in centrosome aberration. We propose that LGALS3BP suppresses assembly of centriolar substructures, and when depleted, causes accumulation of centriolar complexes comprising CPAP, acetylated tubulin and centrin.
中心体的形态和数量在癌细胞中经常失调。在这里，为了确定与癌细胞中心体异常相关的功能因子，我们围绕 23 个中心体和细胞周期调节蛋白建立了一个蛋白质相互作用网络，选择在癌症中失调的相互作用蛋白进行进一步研究。其中一个组件 LGALS3BP 是一种与中心粒和基体相关的蛋白，具有双重作用，当过度表达时会引发中心体肥大，当下调时会导致中心粒亚结构的积累。过表达 LGALS3BP 的 SK-BR-3 癌细胞系表现出肥大的中心体，而在 LGALS3BP 低表达的精原细胞瘤组织中，存在多余的中心粒样结构。在细胞内过表达 LGALS3BP 时，通过耗尽 LGALS3BP 可以逆转中心体肥大，支持其在中心体异常中的直接作用。我们提出，LGALS3BP 抑制中心粒亚结构的组装，当耗尽时，会导致包含 CPAP、乙酰化微管蛋白和中心体蛋白的中心粒复合物的积累。
