PDF(Pubmed)
Abstract：
In cells, signal transduction heavily relies on the intricate regulation of protein kinases, which provide the fundamental framework for modulating most signaling pathways. Dysregulation of kinase activity has been implicated in numerous pathological conditions, particularly in cancer. The druggable nature of most kinases positions them into a focal point during the process of drug development. However, a significant challenge persists, as the role and biological function of nearly one third of human kinases remains largely unknown.Within this diverse landscape, cyclin-dependent kinases (CDKs) emerge as an intriguing molecular subgroup. In human, this kinase family encompasses 21 members, involved in several key biological processes. Remarkably, 13 of these CDKs belong to the category of understudied kinases, and only 5 having undergone broad investigation to date. This knowledge gap underscores the pressing need to delve into the study of these kinases, starting with a comprehensive review of the less-explored ones.Here, we will focus on the PCTAIRE subfamily of CDKs, which includes CDK16, CDK17, and CDK18, arguably among the most understudied CDKs members. To contextualize PCTAIREs within the spectrum of human pathophysiology, we conducted an exhaustive review of the existing literature and examined available databases. This approach resulted in an articulate depiction of these PCTAIREs, encompassing their expression patterns, 3D configurations, mechanisms of activation, and potential functions in normal tissues and in cancer.We propose that this effort offers the possibility of identifying promising areas of future research that extend from basic research to potential clinical and therapeutic applications.
摘要：
在细胞中，信号转导在很大程度上依赖于蛋白激酶的复杂调节，这为调节大多数信号通路提供了基本框架。激酶活性的失调与许多病理状况有关。特别是在癌症中。大多数激酶的药物性质使它们成为药物开发过程中的焦点。然而,一个重大挑战依然存在，因为近三分之一的人类激酶的作用和生物学功能在很大程度上仍然未知。在这个多样化的景观中，细胞周期蛋白依赖性激酶（CDKs）是一个有趣的分子亚群。在人类中,这个激酶家族包含21个成员，参与了几个关键的生物过程。值得注意的是,这些CDK中有13种属于未被研究的激酶类别，到目前为止，只有5人接受了广泛的调查。这种知识差距强调了深入研究这些激酶的迫切需要，从对较少探索的全面审查开始。这里,我们将专注于CDK的PCTAIRE亚家族，其中包括CDK16、CDK17和CDK18，可以说是研究最不足的CDKs成员之一。为了将PCTAIRE置于人类病理生理学范围内，我们对现有文献进行了详尽的回顾,并检查了现有的数据库.这种方法导致了对这些PCTAIRE的清晰描述，包含他们的表达模式，3D配置，激活机制，以及在正常组织和癌症中的潜在功能。我们建议，这项工作为确定从基础研究到潜在的临床和治疗应用的未来研究领域提供了可能性。
