Target type: biologicalprocess
Any process that stops, prevents or reduces the frequency, rate or extent of K48-linked ubiquitination, a protein ubiquitination process in which a polymer of ubiquitin, formed by linkages between lysine residues at position 48 of the ubiquitin monomers, is added to a protein. K48-linked ubiquitination targets the substrate protein for degradation. [GOC:BHF, GOC:rph, PMID:23460740]
Negative regulation of protein K48-linked ubiquitination is a crucial cellular process that controls the stability and activity of proteins. It involves the removal or prevention of K48-linked polyubiquitin chains from target proteins, ultimately leading to their stabilization and preventing their degradation by the proteasome. This process is mediated by a complex interplay of enzymes, including deubiquitinases (DUBs), ubiquitin ligases (E3s), and ubiquitin-binding proteins.
DUBs are a diverse group of enzymes that specifically cleave ubiquitin chains from target proteins. They can recognize and remove K48-linked polyubiquitin chains, thereby preventing proteasomal degradation. DUBs play a critical role in regulating the abundance of proteins involved in various cellular processes, such as cell cycle control, signal transduction, and DNA repair.
E3s are ubiquitin ligases responsible for attaching ubiquitin chains to target proteins. Some E3s can specifically recognize and remove K48-linked polyubiquitin chains, counteracting the ubiquitination process. This activity is crucial for maintaining protein stability and preventing premature degradation.
Ubiquitin-binding proteins can interact with K48-linked polyubiquitin chains, either promoting or inhibiting their removal. Some ubiquitin-binding proteins act as scaffolds, bringing DUBs and their target proteins together, facilitating deubiquitination. Others can block access of DUBs to the ubiquitin chain, preventing its removal.
The regulation of K48-linked ubiquitination is essential for maintaining cellular homeostasis and responding to various stimuli. Dysregulation of this process can lead to various pathological conditions, including cancer, neurodegenerative diseases, and inflammatory disorders. Therefore, understanding the intricate mechanisms governing negative regulation of protein K48-linked ubiquitination is crucial for developing novel therapeutic strategies for these diseases.'
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Protein | Definition | Taxonomy |
---|---|---|
Peptidyl-prolyl cis-trans isomerase A | A peptidyl-prolyl cis-trans isomerase A that is encoded in the genome of human. [PRO:DNx, UniProtKB:P62937] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
2,4-pyridinedicarboxylic acid | lutidinic acid : A pyridinedicarboxylic acid carrying carboxy groups at positions 2 and 4. | pyridinedicarboxylic acid | |
daminozide | daminozide: induces tumors | straight-chain fatty acid | |
prolinal | pyrrolidines | ||
oxalylglycine | N-oxalylglycine : An amino dicarboxylic acid that is iminodiacetic acid with an oxo substituent. It is used as an inhibitor of alpha-ketoglutarate dependent (EC 1.14.11.*) enzymes. oxalylglycine: structure given in first source | amino dicarboxylic acid; N-acylglycine | EC 1.14.11.* (oxidoreductase acting on paired donors, 2-oxoglutarate as one donor, incorporating 1 atom each of oxygen into both donors) inhibitor |
cyclosporine | ramihyphin A: one of the metabolites produced by Fusarium sp. S-435; RN given refers to cpd with unknown MF | homodetic cyclic peptide | anti-asthmatic drug; anticoronaviral agent; antifungal agent; antirheumatic drug; carcinogenic agent; dermatologic drug; EC 3.1.3.16 (phosphoprotein phosphatase) inhibitor; geroprotector; immunosuppressive agent; metabolite |
sanglifehrin a | sanglifehrin A: binds cyclophilin A; isolated from Streptomyces; structure in first source | ||
(melle-4)cyclosporin | (melle-4)cyclosporin: a non-immunosuppressive analog of cyclosporin A | ||
cyclosporin g | cyclosporin G: similar immunosuppressive actions as cyclosporin, but without nephrotoxic side effects; cyclosporin A analog; MW 1217 | ||
scy-635 | |||
alisporivir | alisporivir: nonimmunosuppressive cyclosporin analog; structure/sequence in first source | homodetic cyclic peptide | anticoronaviral agent |