Mannello F, Luchetti F, Falcieri E, Papa S
Istituto di Istologia ed Analisi di Laboratorio, ITOI-CNR, Istituti Ortopedici Rizzoli, Bologna, Italy.
Apoptosis. 2005 Jan;10(1):19-24. doi: 10.1007/s10495-005-6058-7.
Structural, molecular and biochemical approaches have contributed to piecing together the puzzle of how matrix metalloproteinases (MMPs) work and contribute to various disease processes. However, MMPs have many unexpected substrates other than components of the extracellular matrix which profoundly influence cell behaviour, survival and death. With the current understanding of diverse/novel roles of matrix metalloproteinases--particularly their direct or indirect relevance for the early steps during programmed cell death--some seemingly contrasting results seem less surprising. To better target MMPs an appreciation of their many extracellular, intracellular and intranuclear functions, often acting in opposing directions with paradoxical roles in cell death, is carefully required.
结构、分子和生化方法有助于拼凑出基质金属蛋白酶(MMPs)如何发挥作用以及如何促成各种疾病进程的谜团。然而,MMPs除了作用于细胞外基质成分外,还有许多意想不到的底物,这些底物会深刻影响细胞行为、存活和死亡。鉴于目前对基质金属蛋白酶多种不同/新作用的理解,尤其是它们与程序性细胞死亡早期步骤的直接或间接相关性,一些看似相互矛盾的结果似乎就不那么令人惊讶了。为了更好地靶向MMPs,需要仔细了解它们在细胞外、细胞内和细胞核内的多种功能,这些功能在细胞死亡中往往以相反的方向发挥作用,具有自相矛盾的作用。