Perbal B
Laboratoire d'Oncologie Virale et Moléculaire, UFR de Biochimie, Université Paris 7-D, Diderot, France.
Mol Pathol. 2001 Apr;54(2):57-79. doi: 10.1136/mp.54.2.57.
The CCN family of genes presently consists of six distinct members encoding proteins that participate in fundamental biological processes such as cell proliferation, attachment, migration, differentiation, wound healing, angiogenesis, and several pathologies including fibrosis and tumorigenesis. Whereas CYR61 and CTGF were reported to act as positive regulators of cell growth, NOV (nephroblastoma overexpressed) provided the first example of a CCN protein with negative regulatory properties and the first example of aberrant expression being associated with tumour development. The subsequent discovery of the ELM1, rCOP1, and WISP proteins has broadened the variety of functions attributed to the CCN proteins and has extended previous observations to other biological systems. This review discusses fundamental questions regarding the regulation of CCN gene expression in normal and pathological conditions, and the structural basis for their specific biological activity. After discussing the role of nov and other CCN proteins in the development of a variety of different tissues such as kidney, nervous system, muscle, cartilage, and bone, the altered expression of the CCN proteins in various pathologies is discussed, with an emphasis on the altered expression of nov in many different tumour types such as Wilms's tumour, renal cell carcinomas, prostate carcinomas, osteosarcomas, chondrosarcomas, adrenocortical carcinomas, and neuroblastomas. The possible use of nov as a tool for molecular medicine is also discussed. The variety of biological functions attributed to the CCN proteins has led to the proposal of a model in which physical interactions between the amino and carboxy portions of the CCN proteins modulate their biological activity and ensure a proper balance of positive and negative signals through interactions with other partners. In this model, disruption of the secondary structure of the CCN proteins induced by deletions of either terminus is expected to confer on the truncated polypeptide constitutive positive or negative activities.
CCN基因家族目前由六个不同的成员组成，这些成员编码的蛋白质参与细胞增殖、黏附、迁移、分化、伤口愈合、血管生成等基本生物学过程，以及包括纤维化和肿瘤发生在内的多种病理过程。虽然CYR61和CTGF被报道为细胞生长的正调节因子，但NOV（肾母细胞瘤过度表达）是第一个具有负调节特性的CCN蛋白实例，也是异常表达与肿瘤发生相关的第一个实例。随后ELM1、rCOP1和WISP蛋白的发现扩展了赋予CCN蛋白的功能种类，并将先前的观察结果扩展到了其他生物系统。本综述讨论了关于正常和病理条件下CCN基因表达调控的基本问题，以及它们特定生物学活性的结构基础。在讨论了nov和其他CCN蛋白在肾脏、神经系统、肌肉、软骨和骨骼等多种不同组织发育中的作用后，还讨论了CCN蛋白在各种病理情况下的表达改变，重点是nov在多种不同肿瘤类型中的表达改变，如威尔姆斯瘤、肾细胞癌、前列腺癌、骨肉瘤、软骨肉瘤、肾上腺皮质癌和神经母细胞瘤。还讨论了nov作为分子医学工具的可能用途。赋予CCN蛋白的多种生物学功能导致了一个模型的提出，在该模型中，CCN蛋白的氨基和羧基部分之间的物理相互作用调节其生物学活性，并通过与其他伙伴的相互作用确保正负信号的适当平衡。在这个模型中，预计由任何一个末端缺失引起的CCN蛋白二级结构的破坏会赋予截短的多肽组成型的正或负活性。
