Trougakos Ioannis P, Gonos Efstathios S
Laboratory of Molecular & Cellular Aging, Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, 48 Vas Constantinou Avenue, Athens 11635, Greece.
Int J Biochem Cell Biol. 2002 Nov;34(11):1430-48. doi: 10.1016/s1357-2725(02)00041-9.
Clusterin/Apolipoprotein J (ApoJ) is a heterodimeric highly conserved secreted glycoprotein being expressed in a wide variety of tissues and found in all human fluids. Despite being cloned since 1989, no genuine function has been attributed to ApoJ so far. The protein has been reportedly implicated in several diverse physiological processes such as sperm maturation, lipid transportation, complement inhibition, tissue remodeling, membrane recycling, cell-cell and cell-substratum interactions, stabilization of stressed proteins in a folding-competent state and promotion or inhibition of apoptosis. ApoJ gene is differentially regulated by cytokines, growth factors and stress-inducing agents, while another defining prominent and intriguing ApoJ feature is its upregulation in many severe physiological disturbances states and in several neurodegenerative conditions mostly related to advanced aging. Moreover, ApoJ accumulates during the viable growth arrested cellular state of senescence, that is thought to contribute to aging and to tumorigenesis suppression; paradoxically ApoJ is also upregulated in several cases of in vivo cancer progression and tumor formation. This review focuses on the reported data related to ApoJ cell-type and signal specific regulation, function and site of action in normal and cancer cells. We discuss the role of ApoJ during cellular senescence and tumorigenesis, especially under the light of the recently demonstrated various ApoJ intracellular protein forms and their interaction with molecules involved in signal transduction and DNA repair, raising the possibility that its overexpression during cellular senescence might cause a predisposition to cancer.
聚集素/载脂蛋白J（ApoJ）是一种异源二聚体的高度保守的分泌型糖蛋白，在多种组织中表达，并存在于所有人体体液中。尽管自1989年就已克隆出该蛋白，但迄今为止尚未明确其真正功能。据报道，该蛋白参与了多种不同的生理过程，如精子成熟、脂质运输、补体抑制、组织重塑、膜循环利用、细胞间和细胞与基质间的相互作用、使应激蛋白处于可折叠状态的稳定化以及促进或抑制细胞凋亡。ApoJ基因受细胞因子、生长因子和应激诱导剂的差异调节，而另一个突出且引人关注的ApoJ特征是，在许多严重的生理紊乱状态以及一些主要与衰老相关的神经退行性疾病中它会上调。此外，ApoJ在衰老细胞的生长停滞存活状态下会积累，这被认为与衰老和肿瘤发生抑制有关；矛盾的是，在一些体内癌症进展和肿瘤形成的病例中ApoJ也会上调。本综述聚焦于已报道的与ApoJ在正常细胞和癌细胞中的细胞类型及信号特异性调节、功能和作用位点相关的数据。我们讨论了ApoJ在细胞衰老和肿瘤发生过程中的作用，特别是鉴于最近证实的各种ApoJ细胞内蛋白形式及其与参与信号转导和DNA修复的分子的相互作用，这增加了其在细胞衰老过程中过度表达可能导致癌症易感性的可能性。
