Target type: biologicalprocess
Any process that activates or increases the frequency, rate or extent of protein linear polyubiquitination. [GOC:TermGenie, PMID:21931591]
Positive regulation of protein linear polyubiquitination is a complex process that plays a critical role in various cellular functions, including signal transduction, DNA repair, and protein degradation. It involves the attachment of ubiquitin monomers to target proteins in a linear chain, where the ubiquitin molecules are linked through their methionine 1 (Met1) residue to the lysine 48 (Lys48) residue of the next ubiquitin. This specific linkage forms a linear polyubiquitin chain, distinct from other ubiquitin chain topologies.
The process starts with the activation of ubiquitin by the E1 ubiquitin-activating enzyme, which utilizes ATP hydrolysis to generate a high-energy thioester bond between ubiquitin and the E1 enzyme. The activated ubiquitin is then transferred to an E2 ubiquitin-conjugating enzyme, another key player in this pathway.
E3 ubiquitin ligases, the final players in this complex, are responsible for recognizing the target protein and facilitating the transfer of the ubiquitin from the E2 enzyme to the target protein. E3 ligases often exhibit substrate specificity, recognizing specific protein motifs or post-translational modifications on the target protein.
Linear polyubiquitination can be regulated at multiple levels. The expression and activity of E1, E2, and E3 enzymes can be modulated by various mechanisms, including post-translational modifications, protein-protein interactions, and transcriptional regulation.
The formation of linear polyubiquitin chains can be further regulated by deubiquitinases, enzymes that remove ubiquitin chains from proteins. These enzymes can specifically target linear ubiquitin chains, controlling the duration and extent of linear polyubiquitination.
The process of positive regulation of protein linear polyubiquitination involves the enhancement or stimulation of the formation of linear polyubiquitin chains. This can be achieved through increased activity of E1, E2, and E3 enzymes, decreased activity of deubiquitinases, or changes in the accessibility of the target protein to ubiquitination.
Overall, the positive regulation of protein linear polyubiquitination is a tightly regulated process that involves a complex interplay of multiple proteins and enzymes. This precise regulation ensures that linear polyubiquitination occurs only when and where it is needed, allowing for the proper functioning of cellular processes and the maintenance of cellular homeostasis.'
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Protein | Definition | Taxonomy |
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E3 ubiquitin-protein ligase XIAP | A baculoviral IAP repeat-containing protein 4 that is encoded in the genome of human. [PRO:CNA, UniProtKB:P98170] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
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embelin | embelin : A member of the class of dihydroxy-1,4-benzoquinones that is 2,5-dihydroxy-1,4-benzoquinone which is substituted by an undecyl group at position 3. Isolated from Lysimachia punctata and Embelia ribes, it exhibits antimicrobial, antineoplastic and inhibitory activity towards hepatitis C protease. embelin: from Embelia fruit (Myrsinaceae) | dihydroxy-1,4-benzoquinones | antimicrobial agent; antineoplastic agent; hepatitis C protease inhibitor; plant metabolite |
phenylalanine | L-phenylalanine : The L-enantiomer of phenylalanine. phenylalanine : An aromatic amino acid that is alanine in which one of the methyl hydrogens is substituted by a phenyl group. Phenylalanine: An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE. | amino acid zwitterion; erythrose 4-phosphate/phosphoenolpyruvate family amino acid; L-alpha-amino acid; phenylalanine; proteinogenic amino acid | algal metabolite; EC 3.1.3.1 (alkaline phosphatase) inhibitor; Escherichia coli metabolite; human xenobiotic metabolite; micronutrient; mouse metabolite; nutraceutical; plant metabolite; Saccharomyces cerevisiae metabolite |
kaempferol | 7-hydroxyflavonol; flavonols; tetrahydroxyflavone | antibacterial agent; geroprotector; human blood serum metabolite; human urinary metabolite; human xenobiotic metabolite; plant metabolite | |
kaempferol 3-o-rhamnoside | afzelin : A glycosyloxyflavone that is kaempferol attached to an alpha-L-rhamnosyl residue at position 3 via a glycosidic linkage. kaempferol 3-O-rhamnoside: from apple (Malus domestica) leaves; structure in first source | glycosyloxyflavone; monosaccharide derivative; trihydroxyflavone | anti-inflammatory agent; antibacterial agent; plant metabolite |
lbw242 | LBW242: proapoptotic IAP inhibitor; low MW Smac (Second mitochondria-derived activator of caspases) mimetic; structure in first source | ||
sm 164 | SM 164: a bivalent Smac mimetic with antineoplastic activity; structure in first source | benzenes; organic heterobicyclic compound; secondary carboxamide; triazoles | antineoplastic agent; apoptosis inducer; radiosensitizing agent |
lcl161 | 1,3-thiazoles; aromatic ketone; L-alanine derivative; monofluorobenzenes; N-acylpyrrolidine | antineoplastic agent; apoptosis inducer | |
at 406 | |||
gdc-0152 | GDC-0152: structure in first source | ||
birinapant | birinapant: a Smac mimetic with antineoplastic activity | dipeptide | |
nvp-cgm097 | NVP-CGM097: an MDM2 and HDM2 inhibitor; structure in first source | ||
2-carboxyarabinitol 1-phosphate |