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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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Comparison of charge topologies of DWNN and ubiquitin viewed in SPDBviewer. The positive charges are shown in blue while the negative charge is shown in red. Ubiquitin shows an equal charge distribution while DWNN shows a much higher positive charge. This implies that ubiquitin will probably be able to associate with a wider range of proteins due to it having negative and positive areas. Note the diglycine gives a negative charge in both molecules allowing them to associate with the positively charged lysine during modification.
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f2-ijms-13-11804: Comparison of charge topologies of DWNN and ubiquitin viewed in SPDBviewer. The positive charges are shown in blue while the negative charge is shown in red. Ubiquitin shows an equal charge distribution while DWNN shows a much higher positive charge. This implies that ubiquitin will probably be able to associate with a wider range of proteins due to it having negative and positive areas. Note the diglycine gives a negative charge in both molecules allowing them to associate with the positively charged lysine during modification.

Mentions: The recently discovered putative ubiquitin-like modifier DWNN shares about 28% identity with ubiquitin, but together they possess an almost superimposable three-dimensional structure. DWNN is a 76 residue protein found in vertebrates as an N-terminal domain of the Retinoblastoma Binding Protein 6 (RBBP6) family (also known as mouse proliferation potential proteins (P2P-R) or p53-associated cellular protein-testes derived (PACT)) or as an independent module encoded by its own transcript. It lacks the conserved K48 and K63, but in most cases K6 and K29 are conserved [18,104,105]. The residues are not conserved in protists and worms. Although the three-dimensional structure of DWNN is similar to that of ubiquitin the charge topologies are significantly different (Figure 2). Ubiquitin has a much more prominent negative surface compared to DWNN whose surface is largely positively charged. These features suggest that the two domains have different interacting partners. This domain is not found in prokaryotes but is present in all eukaryotes. Similarly, the RBBP6 protein family is found in eukaryotes only and appears to exist as a single copy gene with no transcript variants in plants and in invertebrates.


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

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

Comparison of charge topologies of DWNN and ubiquitin viewed in SPDBviewer. The positive charges are shown in blue while the negative charge is shown in red. Ubiquitin shows an equal charge distribution while DWNN shows a much higher positive charge. This implies that ubiquitin will probably be able to associate with a wider range of proteins due to it having negative and positive areas. Note the diglycine gives a negative charge in both molecules allowing them to associate with the positively charged lysine during modification.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2-ijms-13-11804: Comparison of charge topologies of DWNN and ubiquitin viewed in SPDBviewer. The positive charges are shown in blue while the negative charge is shown in red. Ubiquitin shows an equal charge distribution while DWNN shows a much higher positive charge. This implies that ubiquitin will probably be able to associate with a wider range of proteins due to it having negative and positive areas. Note the diglycine gives a negative charge in both molecules allowing them to associate with the positively charged lysine during modification.
Mentions: The recently discovered putative ubiquitin-like modifier DWNN shares about 28% identity with ubiquitin, but together they possess an almost superimposable three-dimensional structure. DWNN is a 76 residue protein found in vertebrates as an N-terminal domain of the Retinoblastoma Binding Protein 6 (RBBP6) family (also known as mouse proliferation potential proteins (P2P-R) or p53-associated cellular protein-testes derived (PACT)) or as an independent module encoded by its own transcript. It lacks the conserved K48 and K63, but in most cases K6 and K29 are conserved [18,104,105]. The residues are not conserved in protists and worms. Although the three-dimensional structure of DWNN is similar to that of ubiquitin the charge topologies are significantly different (Figure 2). Ubiquitin has a much more prominent negative surface compared to DWNN whose surface is largely positively charged. These features suggest that the two domains have different interacting partners. This domain is not found in prokaryotes but is present in all eukaryotes. Similarly, the RBBP6 protein family is found in eukaryotes only and appears to exist as a single copy gene with no transcript variants in plants and in invertebrates.

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