Garcia-Aranda Marilina, Serrano Alfonso, Redondo Maximino
Department of Biochemistry, REDISSEC, Hospital Costa del Sol, Carretera de Cadiz km, 187, 29600 Marbella. Malaga, Spain.
Department of Biochemistry and Immunology, Universidad de Malaga. Malaga, Spain.
Curr Protein Pept Sci. 2018;19(6):612-622. doi: 10.2174/1389203718666170918155247.
Clusterin is a multifunctional glycoprotein whose role in cells has generated a great controversy in recent years. Since its discovery, numerous studies have linked clusterin expression deregulation with various physio-pathological processes such as cancer or Alzheimer's disease. Although the results of such investigations have sometimes been contradictory, mainly due to the dichotomous role of clusterin isoforms, it has been demonstrated that this protein is involved in diverse cellular processes, including apoptosis, cell cycle regulation, DNA repair or the acquisition of cell resistance against multiple conventional therapies. These results, together with the breakthrough of gene therapies, have motivated a great effort to elucidate the importance of clusterin as a potential therapeutic target. However, the understanding of a single gene, with multiple RNA transcripts and several protein isoforms has turned out to be a complex task. In this review, we summarize the studies published to date on factors that can affect clusterin expression and evaluate if a better understanding of this complex gene/protein would be useful to develop new treatment strategies for cancer and other pathologies.
聚集素是一种多功能糖蛋白，近年来其在细胞中的作用引发了巨大争议。自发现以来，众多研究已将聚集素表达失调与各种生理病理过程联系起来，如癌症或阿尔茨海默病。尽管此类研究结果有时相互矛盾，主要是由于聚集素异构体的双重作用，但已证明该蛋白参与多种细胞过程，包括细胞凋亡、细胞周期调控、DNA修复或细胞对多种传统疗法的抗性获得。这些结果，连同基因疗法的突破，促使人们大力阐明聚集素作为潜在治疗靶点的重要性。然而，要理解一个具有多个RNA转录本和多种蛋白质异构体的单一基因，结果是一项复杂的任务。在本综述中，我们总结了迄今为止发表的关于可影响聚集素表达的因素的研究，并评估对这个复杂的基因/蛋白有更深入的了解是否有助于开发针对癌症和其他病症的新治疗策略。
