Category: Lab Notes: Cancer Biology
Survivin
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Survivin (BIRC5) is a tumour‑specific IAP that integrates apoptosis suppression with essential mitotic functions. As part of the chromosomal passenger complex, Survivin ensures proper chromosome segregation while stabilising anti‑apoptotic pathways, making it a central driver of tumour progression and therapy resistance.
cIAP2
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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
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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.
TRIM Family
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The TRIM family is a large group of single‑chain RING finger ubiquitin ligases that regulate innate immunity, antiviral defence, autophagy, transcription and protein quality control. Defined by their tripartite motif—RING, B‑box and coiled‑coil domains—TRIM proteins use diverse C‑terminal regions to achieve precise substrate specificity. Their roles in immunity, development and cancer make them key regulators of cellular homeostasis.
Cbl‑c
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Cbl‑c is an epithelial‑specific RING finger ubiquitin ligase that regulates EGFR and other receptor tyrosine kinases through targeted ubiquitination. With a streamlined domain architecture and restricted expression pattern, Cbl‑c maintains epithelial homeostasis and prevents excessive RTK signalling. Loss or mutation of Cbl‑c contributes to epithelial cancers, highlighting its importance in growth control and oncogenesis.
Cbl‑b
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Cbl‑b is a single‑chain RING finger ubiquitin ligase that acts as a master regulator of immune activation. By ubiquitinating key signalling molecules in T‑cells, B‑cells and NK cells, Cbl‑b maintains immune tolerance and prevents hyperactivation. Loss of Cbl‑b leads to autoimmunity and enhanced anti‑tumour immunity, making it a critical player in immune homeostasis and a promising target in cancer immunotherapy.
CBL Family Ubiquitin Ligase
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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.
RNF115 (RING Finger Protein 115)
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RNF115 (BCA2) is a dual RING/U‑box E3 ubiquitin ligase that regulates membrane trafficking, innate immunity and antiviral defence. By ubiquitinating BST‑2/Tetherin, Rab7‑associated endosomal proteins and EGFR, RNF115 influences receptor turnover, immune signalling and cancer progression, making it a key regulator of cellular homeostasis.
U‑Box Ubiquitin Ligase
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U‑box ubiquitin ligases are RING‑type E3 enzymes with a modified U‑box domain that enables zinc‑independent ubiquitin transfer. Key members such as CHIP, PRPF19 and UBOX5 regulate chaperone‑mediated protein quality control, DNA‑damage repair and cellular stress responses, making the U‑box family essential for proteostasis and genome stability.
RBR Ubiquitin Ligase
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RBR ubiquitin ligases are hybrid E3 enzymes that combine RING‑type E2 binding with HECT‑like catalytic ubiquitin transfer. Through key members such as Parkin, HHARI and HOIP, the RBR family regulates mitophagy, protein‑quality control and M1‑linked ubiquitination in immune signalling, making them central to cellular stress responses and disease mechanisms.
