Wang Tongtong, Liu Wenqiang, Wang Changfa, Ma Xuelian, Akhtar Muhammad Faheem, Li Yubao, Li Liangliang
College of Agronomy, Liaocheng University, Liaocheng, China.
Veterinary Medicine, Xinjiang Agricultural University, Urumqi, China.
Front Oncol. 2022 Apr 8;12:862206. doi: 10.3389/fonc.2022.862206. eCollection 2022.
The makorin RING finger protein (MKRN) gene family encodes proteins (makorins) with a characteristic array of zinc-finger motifs present in a wide array from invertebrates to vertebrates. MKRNs (MKRN1, MKRN2, MKRN3, MKRN4) as RING finger E3 ligases that mediate substrate degradation are related with conserved RING finger domains that control multiple cellular components the ubiquitin-proteasome system (UPS), including p53, p21, FADD, PTEN, p65, Nptx1, GLK, and some viral or bacterial proteins. MKRNs also served as diverse roles in disease, like MKRN1 in transcription regulation, metabolic disorders, and tumors; MKRN2 in testis physiology, neurogenesis, apoptosis, and mutation of MKRN2 regulation signals transduction, inflammatory responses, melanoma, and neuroblastoma; MKRN3 in central precocious puberty (CPP) therapy; and MKRN4 firstly reported as a novel E3 ligase instead of a pseudogene to contribute to systemic lupus erythematosus (SLE). Here, we systematically review advances in the gene's expression, function, and role of MKRNs orthologs in disease and pathogens infection. Further, MKRNs can be considered targets for the host's innate intracellular antiviral defenses and disease therapy.
Makorin环指蛋白（MKRN）基因家族编码的蛋白质（makorins）具有一系列特征性的锌指基序，广泛存在于从无脊椎动物到脊椎动物的众多生物中。作为介导底物降解的环指E3连接酶，MKRNs（MKRN1、MKRN2、MKRN3、MKRN4）与保守的环指结构域相关，这些结构域控制着多种细胞成分以及泛素-蛋白酶体系统（UPS），包括p53、p21、FADD、PTEN、p65、Nptx1、GLK以及一些病毒或细菌蛋白。MKRNs在疾病中也发挥着多种作用，如MKRN1在转录调控、代谢紊乱和肿瘤方面；MKRN2在睾丸生理学、神经发生、细胞凋亡以及MKRN2调控信号转导的突变、炎症反应、黑色素瘤和神经母细胞瘤方面；MKRN3在中枢性性早熟（CPP）治疗方面；以及MKRN4首次被报道为一种新型E3连接酶而非假基因，与系统性红斑狼疮（SLE）有关。在此，我们系统地综述了MKRNs直系同源物在疾病和病原体感染中的基因表达、功能及作用方面的进展。此外，MKRNs可被视为宿主先天性细胞内抗病毒防御和疾病治疗的靶点。
