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Modification by ubiquitin-like proteins: significance in apoptosis and autophagy pathways.

Cajee UF, Hull R, Ntwasa M - Int J Mol Sci (2012)

Bottom Line: Modifiers such as SUMO, ATG12, ISG15, FAT10, URM1, and UFM have been shown to modify proteins thus conferring functions related to programmed cell death, autophagy and regulation of the immune system.Putative modifiers such as Domain With No Name (DWNN) have been identified in recent times but not fully characterized.We review current progress in targeting these modifiers for drug design strategies.

View Article: PubMed Central - PubMed

Affiliation: School of Molecular & Cell Biology, Gatehouse 512, University of the Witwatersrand, Johannesburg, 2050, South Africa; E-Mails: umar.cajee@students.wits.ac.za (U.-F.C.); rodney.hull@students.wits.ac.za (R.H.).

ABSTRACT
Ubiquitin-like proteins (Ubls) confer diverse functions on their target proteins. The modified proteins are involved in various biological processes, including DNA replication, signal transduction, cell cycle control, embryogenesis, cytoskeletal regulation, metabolism, stress response, homeostasis and mRNA processing. Modifiers such as SUMO, ATG12, ISG15, FAT10, URM1, and UFM have been shown to modify proteins thus conferring functions related to programmed cell death, autophagy and regulation of the immune system. Putative modifiers such as Domain With No Name (DWNN) have been identified in recent times but not fully characterized. In this review, we focus on cellular processes involving human Ubls and their targets. We review current progress in targeting these modifiers for drug design strategies.

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Phylogenetic analysis of ubiquitin-like modifiers and their protein sequence alignment. Protein sequences of the Ubl ubiquitin domains were initially aligned in MEGA 5, using the default ClustalW algorithm. The multiple sequence alignment was then analyzed and tweaked manually to ensure that important conserved residues (lysines, diglycine motif) were accurately aligned. The percentage similarity between each modifier and ubiquitin and the presence of a C-terminal di-glycine are marked on the phylogenetic tree (A). DWNN belongs to the group with proteins that have higher sequence identity with ubiquitin but it is the most distantly related in this group. The more distantly related UFM, Atg8 and Atg12 lack the conserved diglycine.
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f1-ijms-13-11804: Phylogenetic analysis of ubiquitin-like modifiers and their protein sequence alignment. Protein sequences of the Ubl ubiquitin domains were initially aligned in MEGA 5, using the default ClustalW algorithm. The multiple sequence alignment was then analyzed and tweaked manually to ensure that important conserved residues (lysines, diglycine motif) were accurately aligned. The percentage similarity between each modifier and ubiquitin and the presence of a C-terminal di-glycine are marked on the phylogenetic tree (A). DWNN belongs to the group with proteins that have higher sequence identity with ubiquitin but it is the most distantly related in this group. The more distantly related UFM, Atg8 and Atg12 lack the conserved diglycine.

Mentions: There are nine phylogenetically distinct classes of Ubls including SUMO, NEDD8, ISG15, FUB1, FAT10, Atg8, Atg12, Urm1, and Ufm1. We report here the existence of a putative modifier known as DWNN whose characteristics resemble those of Ubls but with poorly defined biochemical and functional features (Table 1). Ubls are involved in cellular activities such as apoptosis, autophagy and signaling pathways that mediate biological processes like cell proliferation, immune response and development. Ubls share low primary sequence similarity but phylogenetic analysis shows some evolutionary relatedness and clustering albeit with weak nodes (Figure 1). The most common feature is their three-dimensional fold.


Modification by ubiquitin-like proteins: significance in apoptosis and autophagy pathways.

Cajee UF, Hull R, Ntwasa M - Int J Mol Sci (2012)

Phylogenetic analysis of ubiquitin-like modifiers and their protein sequence alignment. Protein sequences of the Ubl ubiquitin domains were initially aligned in MEGA 5, using the default ClustalW algorithm. The multiple sequence alignment was then analyzed and tweaked manually to ensure that important conserved residues (lysines, diglycine motif) were accurately aligned. The percentage similarity between each modifier and ubiquitin and the presence of a C-terminal di-glycine are marked on the phylogenetic tree (A). DWNN belongs to the group with proteins that have higher sequence identity with ubiquitin but it is the most distantly related in this group. The more distantly related UFM, Atg8 and Atg12 lack the conserved diglycine.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3472776&req=5

f1-ijms-13-11804: Phylogenetic analysis of ubiquitin-like modifiers and their protein sequence alignment. Protein sequences of the Ubl ubiquitin domains were initially aligned in MEGA 5, using the default ClustalW algorithm. The multiple sequence alignment was then analyzed and tweaked manually to ensure that important conserved residues (lysines, diglycine motif) were accurately aligned. The percentage similarity between each modifier and ubiquitin and the presence of a C-terminal di-glycine are marked on the phylogenetic tree (A). DWNN belongs to the group with proteins that have higher sequence identity with ubiquitin but it is the most distantly related in this group. The more distantly related UFM, Atg8 and Atg12 lack the conserved diglycine.
Mentions: There are nine phylogenetically distinct classes of Ubls including SUMO, NEDD8, ISG15, FUB1, FAT10, Atg8, Atg12, Urm1, and Ufm1. We report here the existence of a putative modifier known as DWNN whose characteristics resemble those of Ubls but with poorly defined biochemical and functional features (Table 1). Ubls are involved in cellular activities such as apoptosis, autophagy and signaling pathways that mediate biological processes like cell proliferation, immune response and development. Ubls share low primary sequence similarity but phylogenetic analysis shows some evolutionary relatedness and clustering albeit with weak nodes (Figure 1). The most common feature is their three-dimensional fold.

Bottom Line: Modifiers such as SUMO, ATG12, ISG15, FAT10, URM1, and UFM have been shown to modify proteins thus conferring functions related to programmed cell death, autophagy and regulation of the immune system.Putative modifiers such as Domain With No Name (DWNN) have been identified in recent times but not fully characterized.We review current progress in targeting these modifiers for drug design strategies.

View Article: PubMed Central - PubMed

Affiliation: School of Molecular & Cell Biology, Gatehouse 512, University of the Witwatersrand, Johannesburg, 2050, South Africa; E-Mails: umar.cajee@students.wits.ac.za (U.-F.C.); rodney.hull@students.wits.ac.za (R.H.).

ABSTRACT
Ubiquitin-like proteins (Ubls) confer diverse functions on their target proteins. The modified proteins are involved in various biological processes, including DNA replication, signal transduction, cell cycle control, embryogenesis, cytoskeletal regulation, metabolism, stress response, homeostasis and mRNA processing. Modifiers such as SUMO, ATG12, ISG15, FAT10, URM1, and UFM have been shown to modify proteins thus conferring functions related to programmed cell death, autophagy and regulation of the immune system. Putative modifiers such as Domain With No Name (DWNN) have been identified in recent times but not fully characterized. In this review, we focus on cellular processes involving human Ubls and their targets. We review current progress in targeting these modifiers for drug design strategies.

Show MeSH