Institut de Biotecnologia i Biomedicina, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Cerdanyola del Vallés, 08193 Barcelona, Spain.
Cells. 2023 Jan 5;12(2):235. doi: 10.3390/cells12020235.
The term moonlighting proteins refers to those proteins that present alternative functions performed by a single polypeptide chain acquired throughout evolution (called canonical and moonlighting, respectively). Over 78% of moonlighting proteins are involved in human diseases, 48% are targeted by current drugs, and over 25% of them are involved in the virulence of pathogenic microorganisms. These facts encouraged us to study the link between the functions of moonlighting proteins and disease. We found a large number of moonlighting functions activated by pathological conditions that are highly involved in disease development and progression. The factors that activate some moonlighting functions take place only in pathological conditions, such as specific cellular translocations or changes in protein structure. Some moonlighting functions are involved in disease promotion while others are involved in curbing it. The disease-impairing moonlighting functions attempt to restore the homeostasis, or to reduce the damage linked to the imbalance caused by the disease. The disease-promoting moonlighting functions primarily involve the immune system, mesenchyme cross-talk, or excessive tissue proliferation. We often find moonlighting functions linked to the canonical function in a pathological context. Moonlighting functions are especially coordinated in inflammation and cancer. Wound healing and epithelial to mesenchymal transition are very representative. They involve multiple moonlighting proteins with a different role in each phase of the process, contributing to the current-phase phenotype or promoting a phase switch, mitigating the damage or intensifying the remodeling. All of this implies a new level of complexity in the study of pathology genesis, progression, and treatment. The specific protein function involved in a patient's progress or that is affected by a drug must be elucidated for the correct treatment of diseases.
术语“兼职蛋白”是指那些在进化过程中通过单一多肽链获得的具有替代功能的蛋白质（分别称为经典功能和兼职功能）。超过 78%的兼职蛋白与人类疾病有关，48%的蛋白被现有药物靶向，超过 25%的蛋白与致病微生物的毒力有关。这些事实促使我们研究兼职蛋白的功能与疾病之间的联系。我们发现了大量由病理条件激活的兼职功能，这些功能与疾病的发展和进展高度相关。激活某些兼职功能的因素仅在病理条件下发生，例如特定的细胞易位或蛋白质结构的变化。一些兼职功能参与疾病的促进，而另一些则参与疾病的抑制。损害疾病的兼职功能试图恢复体内平衡，或减轻与疾病引起的失衡相关的损伤。促进疾病的兼职功能主要涉及免疫系统、间质细胞相互作用或过度组织增殖。我们经常发现兼职功能与病理条件下的经典功能有关。兼职功能在炎症和癌症中特别协调。伤口愈合和上皮间质转化就是非常典型的例子。它们涉及多个兼职蛋白，在该过程的每个阶段具有不同的作用，有助于当前阶段的表型或促进阶段转换，减轻损伤或加强重塑。所有这些都意味着在研究病理学发生、进展和治疗方面出现了一个新的复杂性水平。为了正确治疗疾病，必须阐明参与患者进展或受药物影响的特定蛋白质功能。
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