The emerging role of Deubiquitinases (DUBs) in parasites: A foresight review

被引:8
|
作者
Kumar, Prakash [1 ]
Kumar, Pawan [1 ]
Mandal, Debabrata [1 ]
Velayutham, Ravichandiran [1 ,2 ]
机构
[1] Natl Inst Pharmaceut Educ & Res, Dept Biotechnol, Hajipur, India
[2] Natl Inst Pharmaceut Educ & Res, Kolkata, India
关键词
deubiquitination; parasitic disease; drug target; in-silico analysis; ubiquitin; USP; DUB domains; TRICHINELLA-SPIRALIS; CRYSTAL-STRUCTURE; SUBSTRATE-SPECIFICITY; PROTEIN MODIFICATIONS; CYSTEINE PROTEASE; CATALYTIC DOMAIN; STRUCTURAL BASIS; UBIQUITIN; ENZYME; EXPRESSION;
D O I
10.3389/fcimb.2022.985178
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Before the discovery of the proteasome complex, the lysosomes with acidic proteases and caspases in apoptotic pathways were thought to be the only pathways for the degradation of damaged, unfolded, and aged proteins. However, the discovery of 26S and 20S proteasome complexes in eukaryotes and microbes, respectively, established that the degradation of most proteins is a highly regulated ATP-dependent pathway that is significantly conserved across each domain of life. The proteasome is part of the ubiquitin-proteasome system (UPS), where the covalent tagging of a small molecule called ubiquitin (Ub) on the proteins marks its proteasomal degradation. The type and chain length of ubiquitination further determine whether a protein is designated for further roles in multi-cellular processes like DNA repair, trafficking, signal transduction, etc., or whether it will be degraded by the proteasome to recycle the peptides and amino acids. Deubiquitination, on the contrary, is the removal of ubiquitin from its substrate molecule or the conversion of polyubiquitin chains into monoubiquitin as a precursor to ubiquitin. Therefore, deubiquitylating enzymes (DUBs) can maintain the dynamic state of cellular ubiquitination by releasing conjugated ubiquitin from proteins and controlling many cellular pathways that are essential for their survival. Many DUBs are well characterized in the human system with potential drug targets in different cancers. Although, proteasome complex and UPS of parasites, like plasmodium and leishmania, were recently coined as multi-stage drug targets the role of DUBs is completely unexplored even though structural domains and functions of many of these parasite DUBs are conserved having high similarity even with its eukaryotic counterpart. This review summarizes the identification & characterization of different parasite DUBs based on in silico and a few functional studies among different phylogenetic classes of parasites including Metazoan (Schistosoma, Trichinella), Apicomplexan protozoans (Plasmodium, Toxoplasma, Eimeria, Cryptosporidium), Kinetoplastidie (Leishmania, Trypanosoma) and Microsporidia (Nosema). The identification of different homologs of parasite DUBs with structurally similar domains with eukaryotes, and the role of these DUBs alone or in combination with the 20S proteosome complex in regulating the parasite survival/death is further elaborated. We propose that small molecules/inhibitors of human DUBs can be potential antiparasitic agents due to their significant structural conservation.
引用
收藏
页数:17
相关论文
共 50 条
  • [41] Foresight of evolving security threats posed by emerging technologies
    Hauptman, Aharon
    Sharan, Yair
    FORESIGHT, 2013, 15 (05): : 375 - 391
  • [42] The Emerging Role for RNA Polymerase II in Regulating Virulence Gene Expression in Malaria Parasites
    Ukaegbu, Uchechi E.
    Deitsch, Kirk W.
    PLOS PATHOGENS, 2015, 11 (07)
  • [43] A Review of the Emerging Role of Silk for the Treatment of the Eye
    Simon H. Tran
    Clive G. Wilson
    F. Philipp Seib
    Pharmaceutical Research, 2018, 35
  • [44] The emerging role of adipokines in osteoarthritis: a narrative review
    Hu, Peng-fei
    Bao, Jia-peng
    Wu, Li-dong
    MOLECULAR BIOLOGY REPORTS, 2011, 38 (02) : 873 - 878
  • [45] The emerging role of adipokines in osteoarthritis: a narrative review
    Peng-fei Hu
    Jia-peng Bao
    Li-dong Wu
    Molecular Biology Reports, 2011, 38 : 873 - 878
  • [46] A review of HPRT and its emerging role in cancer
    Townsend, Michelle H.
    Robison, Richard A.
    O'Neill, Kim L.
    MEDICAL ONCOLOGY, 2018, 35 (06)
  • [47] An emerging role of cGMP in the treatment of schizophrenia: A review
    Shim, Seong
    Shuman, Michael
    Duncan, Erica
    SCHIZOPHRENIA RESEARCH, 2016, 170 (01) : 226 - 231
  • [48] Emerging role of lncRNAs in osteoarthritis: An updated review
    Wang, Rongliang
    Shiu, Hoi Ting
    Lee, Wayne Yuk Wai
    FRONTIERS IN IMMUNOLOGY, 2022, 13
  • [49] Emerging role of ferroptosis in diabetic retinopathy: a review
    Wang, Ruohong
    Rao, Suyun
    Zhong, Zheng
    Xiao, Ke
    Chen, Xuhui
    Sun, Xufang
    JOURNAL OF DRUG TARGETING, 2024, 32 (04) : 393 - 403
  • [50] Emerging Role of Terpenoids for the Treatment of Cancer: A Review
    Chopra, Bhawna
    Dhingra, Ashwani Kumar
    Dhar, Kanaya Lal
    Nepali, Kunal
    MINI-REVIEWS IN MEDICINAL CHEMISTRY, 2021, 21 (16) : 2300 - 2336