Dickinson D P
Medical College of Georgia, School of Dentistry, Department of Oral Biology, and Maxillofacial Pathology, Augusta 30912, USA.
Crit Rev Oral Biol Med. 2002;13(3):238-75. doi: 10.1177/154411130201300304.
Cysteine peptidases (CPs) are phylogenetically ubiquitous enzymes that can be classified into clans of evolutionarily independent proteins based on the structural organization of the active site. In mammals, two of the major clans represented in the genome are: the CA clan, whose members share a structure and evolutionary history with papain; and the CD clan, which includes the legumains and caspases. This review focuses on the properties of these enzymes, with an emphasis on their potential roles in the oral cavity. The human genome encodes at least (but possibly no more than) 11 distinct enzymes, called cathepsins, that are members of the papain family C1A. Ten of these are present in rodents, which also carry additional genes encoding other cathepsins and cathepsin-like proteins. Human cathepsins are best known from the ubiquitously expressed lysosomal cathepsins B, H, and L, and dipeptidyl peptidase I (DPP I), which until recently were considered to mediate primarily "housekeeping" functions in the cell. However, mutations in DPP I have now been shown to underlie Papillon-Lefevre syndrome and pre-pubertal periodontitis. Other cathepsins are involved in tissue-specific functions such as bone remodeling, but relatively little is known about the functions of several recently discovered enzymes. Collectively, CPs participate in multiple host systems that are active in health and in disease. They are involved in tissue remodeling and turnover of the extracellular matrix, immune system function, and modulation and alteration of cell function. Intracellularly, CPs function in diverse processes including normal protein turnover, antigen and proprotein processing, and apoptosis. Extracellularly, they can contribute directly to the degradation of foreign proteins and the extracellular matrix. However, CPs can also participate in proteolytic cascades that amplify the degradative capacity, potentially leading to pathological damage, and facilitating the penetration of tissues by cancer cells. We know relatively little regarding the role of human CPs in the oral cavity in health or disease. Most studies to date have focused on the potential use of the lysosomal enzymes as markers for periodontal disease activity. Human saliva contains high levels of cystatins, which are potent CP inhibitors. Although these proteins are presumed to serve a protective function, their in vivo targets are unknown, and it remains to be discovered whether they serve to control any human CP activity.
半胱氨酸蛋白酶（CPs）是在系统发育上广泛存在的酶，根据活性位点的结构组织，可分为进化上独立的蛋白质家族。在哺乳动物中，基因组中代表的两个主要家族是：CA家族，其成员与木瓜蛋白酶具有相同的结构和进化历史；以及CD家族，其中包括豆球蛋白和半胱天冬酶。本综述重点关注这些酶的特性，尤其强调它们在口腔中的潜在作用。人类基因组编码至少（但可能不超过）11种不同的酶，称为组织蛋白酶，它们是木瓜蛋白酶家族C1A的成员。其中10种存在于啮齿动物中，啮齿动物还携带编码其他组织蛋白酶和组织蛋白酶样蛋白的额外基因。人类组织蛋白酶最广为人知的是普遍表达的溶酶体组织蛋白酶B、H和L，以及二肽基肽酶I（DPP I），直到最近它们还被认为主要在细胞中介导“管家”功能。然而，现在已经证明DPP I中的突变是帕皮永-勒费夫尔综合征和青春期前牙周炎的基础。其他组织蛋白酶参与组织特异性功能，如骨重塑，但对几种最近发现的酶的功能了解相对较少。总的来说，CPs参与了多个在健康和疾病中起作用的宿主系统。它们参与组织重塑和细胞外基质的更新、免疫系统功能以及细胞功能的调节和改变。在细胞内，CPs在多种过程中发挥作用，包括正常的蛋白质更新、抗原和前体蛋白加工以及细胞凋亡。在细胞外，它们可以直接促进外源蛋白和细胞外基质的降解。然而，CPs也可以参与蛋白水解级联反应，放大降解能力，潜在地导致病理损伤，并促进癌细胞对组织的侵袭。我们对人类CPs在口腔健康或疾病中的作用了解相对较少。迄今为止，大多数研究都集中在溶酶体酶作为牙周疾病活动标志物的潜在用途上。人类唾液中含有高水平的胱抑素，它们是有效的CP抑制剂。尽管这些蛋白质被认为具有保护作用，但其体内靶点尚不清楚，它们是否用于控制任何人类CP活性仍有待发现。
