Note for: Ubiquitin and its complexity!!
Ubiquitin chain diversity at a glance
(doi: 10.1242/jcs.183954)
Human Ub (76 amino acids)--> 7 Lys
Since I have worked with E3 ubiquitin ligase, I need to read and recall a lot on the ubiquitin. The last time that I could recall from molecular biology was that the ubiquitination was for the protein degradation. Nowadays, with the advantage of the technology, they are not meant to function only as proteasomal degradation, besides, it involves diverse kinds of functions, for example, endocytosis, DNA repair and subcellular localization.
Things are even more complicated when it is found out that ubiquitin can be subjected to modifications, phosphorylation (Ub-P) and acetylation (Ub-Ac)!! I have not kept track on this yet. but I will try to update how it relates to the cellular process and also whether it causes the disease.
Ubiquitylation is a reversible process, another enzyme that reversibly function is deubiquitylating (DUB) enzyme.
Ubiquitin code:
K6-linkage--it is unclear yet. There was the research showed that it indirectly involved with DNA repair through the heterodimeric interaction between BRCA1-BARD1.
K11-linkage--drive proteasomal degradation and mitotic exit through the activity of APC/C (anaphase-promoting complex). Many more studies are needed to be done. Not only poly-K11, sounds to me it relates to the branched structure of polyubiquitin (through K48--heterotypic).
K27-linkage--this type of linkage involves with DNA damage response. Besides the phosphorylation of H2Ax, forming the polyubiquitination through the K27 linkage also recruits the downstream mediators to amplify the signal and execute the appropriated repair. Moreover, this type of linkage involves the immune response toward the invasion of foreign DNA from microorganisms.
K29-linkage--it relates to protein involves in the wnt signaling pathway by which Axin can be polyubiquitylated (poly K29), thus interfering the interaction of LPR5/6 and reduce the wnt signal.
K63-linkage--it participates in the protein sorting; both endocytic and secretory pathways.
M1-linkage--it plays roles in the inflammatory and immune responses. It regulates the activation of TF NF-kB.
Phospho-ubiquitin (post-post-translational modification!!)--it participates in the mitophagy which is the process to get rid of malfunction of mitochondria. By adding phosphate group to ubiquitin can signal the cell to recruit the autophagic machinery to digest bad mitochondria.
very good and precise poster for the diverse functions of ubiquitin-tagging.
At the very end;
The study of complexity and diversity of ubiquitin requires good mass spectrometric techniques to reveal the cellular functions. Structural information of UBDs (ubiquitin binding domain) and DUBs (deubiquitination) also aid us to understand how they recognize the linkage patterns of ubiquitin. E3 ligase and DUB will be the most exploring field since it deals with substrate specificity and it is the final step to execute the cellular functions.
(doi: 10.1242/jcs.183954)
Human Ub (76 amino acids)--> 7 Lys
· MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGG
Things are even more complicated when it is found out that ubiquitin can be subjected to modifications, phosphorylation (Ub-P) and acetylation (Ub-Ac)!! I have not kept track on this yet. but I will try to update how it relates to the cellular process and also whether it causes the disease.
Ubiquitylation is a reversible process, another enzyme that reversibly function is deubiquitylating (DUB) enzyme.
Ubiquitin code:
K6-linkage--it is unclear yet. There was the research showed that it indirectly involved with DNA repair through the heterodimeric interaction between BRCA1-BARD1.
K11-linkage--drive proteasomal degradation and mitotic exit through the activity of APC/C (anaphase-promoting complex). Many more studies are needed to be done. Not only poly-K11, sounds to me it relates to the branched structure of polyubiquitin (through K48--heterotypic).
K27-linkage--this type of linkage involves with DNA damage response. Besides the phosphorylation of H2Ax, forming the polyubiquitination through the K27 linkage also recruits the downstream mediators to amplify the signal and execute the appropriated repair. Moreover, this type of linkage involves the immune response toward the invasion of foreign DNA from microorganisms.
K29-linkage--it relates to protein involves in the wnt signaling pathway by which Axin can be polyubiquitylated (poly K29), thus interfering the interaction of LPR5/6 and reduce the wnt signal.
K63-linkage--it participates in the protein sorting; both endocytic and secretory pathways.
M1-linkage--it plays roles in the inflammatory and immune responses. It regulates the activation of TF NF-kB.
Phospho-ubiquitin (post-post-translational modification!!)--it participates in the mitophagy which is the process to get rid of malfunction of mitochondria. By adding phosphate group to ubiquitin can signal the cell to recruit the autophagic machinery to digest bad mitochondria.
very good and precise poster for the diverse functions of ubiquitin-tagging.
At the very end;
The study of complexity and diversity of ubiquitin requires good mass spectrometric techniques to reveal the cellular functions. Structural information of UBDs (ubiquitin binding domain) and DUBs (deubiquitination) also aid us to understand how they recognize the linkage patterns of ubiquitin. E3 ligase and DUB will be the most exploring field since it deals with substrate specificity and it is the final step to execute the cellular functions.
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