regulation of ubiquitin-protein transferase activity / epithelial cell maturation involved in prostate gland development / branching involved in prostate gland morphogenesis / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / regulation of DNA damage checkpoint / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway ...regulation of ubiquitin-protein transferase activity / epithelial cell maturation involved in prostate gland development / branching involved in prostate gland morphogenesis / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / regulation of DNA damage checkpoint / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / target-directed miRNA degradation / elongin complex / VCB complex / positive regulation of protein autoubiquitination / death receptor binding / protein neddylation / regulation of extrinsic apoptotic signaling pathway via death domain receptors / negative regulation of non-canonical NF-kappaB signal transduction / NEDD8 ligase activity / Cul5-RING ubiquitin ligase complex / negative regulation of response to oxidative stress / ubiquitin-ubiquitin ligase activity / Cul4A-RING E3 ubiquitin ligase complex / SCF ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / negative regulation of type I interferon production / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul3-RING ubiquitin ligase complex / Prolactin receptor signaling / protein monoubiquitination / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / cullin family protein binding / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / ubiquitin-like ligase-substrate adaptor activity / Tat-mediated elongation of the HIV-1 transcript / Formation of HIV-1 elongation complex containing HIV-1 Tat / Formation of HIV elongation complex in the absence of HIV Tat / Nuclear events stimulated by ALK signaling in cancer / protein K48-linked ubiquitination / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / positive regulation of TORC1 signaling / RNA Polymerase II Pre-transcription Events / T cell activation / regulation of cellular response to insulin stimulus / Regulation of BACH1 activity / intrinsic apoptotic signaling pathway / post-translational protein modification / transcription corepressor binding / Degradation of DVL / transcription elongation by RNA polymerase II / TP53 Regulates Transcription of DNA Repair Genes / Recognition of DNA damage by PCNA-containing replication complex / transcription initiation at RNA polymerase II promoter / Degradation of GLI1 by the proteasome / Negative regulation of NOTCH4 signaling / cellular response to amino acid stimulus / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Vif-mediated degradation of APOBEC3G / Hedgehog 'on' state / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / DNA Damage Recognition in GG-NER / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / RING-type E3 ubiquitin transferase / Degradation of beta-catenin by the destruction complex / negative regulation of canonical Wnt signaling pathway / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Inactivation of CSF3 (G-CSF) signaling / Dual Incision in GG-NER / Evasion by RSV of host interferon responses / NOTCH1 Intracellular Domain Regulates Transcription / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Formation of TC-NER Pre-Incision Complex / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / Regulation of expression of SLITs and ROBOs / Formation of Incision Complex in GG-NER / Interleukin-1 signaling / Orc1 removal from chromatin / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / G1/S transition of mitotic cell cycle / Regulation of RAS by GAPs / protein polyubiquitination / positive regulation of protein catabolic process / ubiquitin-protein transferase activity / Regulation of RUNX2 expression and activity / cellular response to UV / KEAP1-NFE2L2 pathway / MAPK cascade / ubiquitin protein ligase activity / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / protein-macromolecule adaptor activity 類似検索 - 分子機能
National Natural Science Foundation of China (NSFC)
81621063, 31800626
中国
引用
ジャーナル: EMBO J / 年: 2024 タイトル: Structural insights into the ubiquitylation strategy of the oligomeric CRL2 E3 ubiquitin ligase. 著者: Zonglin Dai / Ling Liang / Weize Wang / Peng Zuo / Shang Yu / Yaqi Liu / Xuyang Zhao / Yishuo Lu / Yan Jin / Fangting Zhang / Dian Ding / Weiwei Deng / Yuxin Yin / 要旨: Cullin-RING E3 ubiquitin ligase (CRL) family members play critical roles in numerous biological processes and diseases including cancer and Alzheimer's disease. Oligomerization of CRLs has been ...Cullin-RING E3 ubiquitin ligase (CRL) family members play critical roles in numerous biological processes and diseases including cancer and Alzheimer's disease. Oligomerization of CRLs has been reported to be crucial for the regulation of their activities. However, the structural basis for its regulation and mechanism of its oligomerization are not fully known. Here, we present cryo-EM structures of oligomeric CRL2 in its unneddylated state, neddylated state in complex with BEX2 as well as neddylated state in complex with FNIP1/FLCN. These structures reveal that asymmetric dimerization of N8-CRL2 is critical for the ubiquitylation of BEX2 while FNIP1/FLCN is ubiquitylated by monomeric CRL2. Our data present an example of the asymmetric homo-dimerization of CRL. Taken together, this study sheds light on the ubiquitylation strategy of oligomeric CRL2 according to substrates with different scales.