Tag: Ubiquitination
Post-Translational Modification
Post-translational modifications (PTMs) are biochemical changes that occur during or after protein synthesis and regulate protein structure, activity, stability, localization, interactions, and degradation. This overview introduces the major types of PTMs, their biological functions, mechanisms, role in disease, and methods used to study protein modifications.
IAP Family
The IAP family consists of intracellular proteins that regulate apoptosis, ubiquitination and immune signalling. Through their BIR domains and RING ligase activity, IAPs control caspase inhibition, NF‑κB activation, inflammasome signalling and tumour cell survival, making them central players in cell biology and cancer research.
XIAP
XIAP is the most potent endogenous inhibitor of caspases and a central regulator of apoptosis and immune signalling. Through its BIR domains and RING ubiquitin ligase activity, XIAP blocks caspase‑3, caspase‑7 and caspase‑9 while modulating NF‑κB pathways, making it a key player in cancer, inflammation and immune disorders.
Livin (ML‑IAP)
Livin (ML‑IAP) is a tumour‑specific inhibitor of apoptosis that blocks caspase activity and ubiquitinates pro‑apoptotic proteins. Its splice variants, Livin‑α and Livin‑β, differ in potency, and its unique ability to switch from anti‑apoptotic to pro‑apoptotic after cleavage makes Livin a key regulator of tumour survival and therapy resistance.
cIAP2
cIAP2 is a ubiquitin ligase that regulates TNF receptor signalling, non‑canonical NF‑κB activation and NOD2‑mediated immune responses. By controlling RIPK1, RIPK2 and NIK stability, cIAP2 determines whether cells activate survival pathways or transition into apoptosis, making it essential in inflammation and cancer biology.
cIAP1
cIAP1 is a ubiquitin ligase that regulates TNF receptor signalling and determines whether cells activate NF‑κB survival pathways or switch into apoptosis or necroptosis. By controlling RIPK1 ubiquitination and cooperating with TRAF2, cIAP1 plays essential roles in inflammation, immunity and cancer biology.
CBL Family Ubiquitin Ligase
The CBL family of ubiquitin ligases—c‑Cbl, Cbl‑b and Cbl‑c—are single‑chain RING finger E3 enzymes that regulate receptor tyrosine kinase signalling, immune activation and epithelial homeostasis. Through their TKB and RING domains, CBL proteins control ubiquitination, endocytosis and signal attenuation. Dysregulation of CBL ligases contributes to cancer, autoimmunity and inflammatory disorders, highlighting their importance in cellular regulation and disease.
Proteasome
The proteasome is the cell’s primary protein degradation machinery, responsible for eliminating damaged and regulatory proteins. This comprehensive guide covers its structure, the ubiquitin-tagging process, its role in neurodegeneration and cancer, and the development of proteasome inhibitors like bortezomib for cancer therapy.
RING Finger Ubiquitin Ligase
RING finger ubiquitin ligases are the largest class of E3 enzymes in the ubiquitin–proteasome system, defined by a zinc‑binding cross‑brace RING domain that positions E2~Ub for direct ubiquitin transfer. They regulate essential cellular processes including cell cycle progression, DNA repair, immunity, and neuronal function. Dysregulation of RING and RBR ligases such as MDM2 and Parkin contributes to cancer and neurodegeneration, while modern PROTAC therapeutics harness CRL4^CRBN and CRL2^VHL complexes to redirect ubiquitination toward disease‑associated proteins.
Post-Translational Modification
Post-translational modifications (PTMs) are biochemical changes that occur during or after protein synthesis and regulate protein structure, activity, stability, localization, interactions, and degradation. This overview introduces the major types of PTMs, their biological functions, mechanisms, role in disease, and methods used to study protein modifications.
IAP Family
The IAP family consists of intracellular proteins that regulate apoptosis, ubiquitination and immune signalling. Through their BIR domains and RING ligase activity, IAPs control caspase inhibition, NF‑κB activation, inflammasome signalling and tumour cell survival, making them central players in cell biology and cancer research.
XIAP
XIAP is the most potent endogenous inhibitor of caspases and a central regulator of apoptosis and immune signalling. Through its BIR domains and RING ubiquitin ligase activity, XIAP blocks caspase‑3, caspase‑7 and caspase‑9 while modulating NF‑κB pathways, making it a key player in cancer, inflammation and immune disorders.
Livin (ML‑IAP)
Livin (ML‑IAP) is a tumour‑specific inhibitor of apoptosis that blocks caspase activity and ubiquitinates pro‑apoptotic proteins. Its splice variants, Livin‑α and Livin‑β, differ in potency, and its unique ability to switch from anti‑apoptotic to pro‑apoptotic after cleavage makes Livin a key regulator of tumour survival and therapy resistance.
cIAP2
cIAP2 is a ubiquitin ligase that regulates TNF receptor signalling, non‑canonical NF‑κB activation and NOD2‑mediated immune responses. By controlling RIPK1, RIPK2 and NIK stability, cIAP2 determines whether cells activate survival pathways or transition into apoptosis, making it essential in inflammation and cancer biology.
cIAP1
cIAP1 is a ubiquitin ligase that regulates TNF receptor signalling and determines whether cells activate NF‑κB survival pathways or switch into apoptosis or necroptosis. By controlling RIPK1 ubiquitination and cooperating with TRAF2, cIAP1 plays essential roles in inflammation, immunity and cancer biology.
CBL Family Ubiquitin Ligase
The CBL family of ubiquitin ligases—c‑Cbl, Cbl‑b and Cbl‑c—are single‑chain RING finger E3 enzymes that regulate receptor tyrosine kinase signalling, immune activation and epithelial homeostasis. Through their TKB and RING domains, CBL proteins control ubiquitination, endocytosis and signal attenuation. Dysregulation of CBL ligases contributes to cancer, autoimmunity and inflammatory disorders, highlighting their importance in cellular regulation and disease.
Proteasome
The proteasome is the cell’s primary protein degradation machinery, responsible for eliminating damaged and regulatory proteins. This comprehensive guide covers its structure, the ubiquitin-tagging process, its role in neurodegeneration and cancer, and the development of proteasome inhibitors like bortezomib for cancer therapy.
RING Finger Ubiquitin Ligase
RING finger ubiquitin ligases are the largest class of E3 enzymes in the ubiquitin–proteasome system, defined by a zinc‑binding cross‑brace RING domain that positions E2~Ub for direct ubiquitin transfer. They regulate essential cellular processes including cell cycle progression, DNA repair, immunity, and neuronal function. Dysregulation of RING and RBR ligases such as MDM2 and Parkin contributes to cancer and neurodegeneration, while modern PROTAC therapeutics harness CRL4^CRBN and CRL2^VHL complexes to redirect ubiquitination toward disease‑associated proteins.