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Part of an E3 ubiquitin ligase complex for neddylation. Promotes neddylation of cullin components of E3 cullin-RING ubiquitin ligase complexes. Acts by binding to cullin-RBX1 complexes in the cytoplasm and promoting their nuclear translocation, enhancing recruitment of E2-NEDD8 (UBE2M-NEDD8) thioester to the complex, and optimizing the orientation of proteins in the complex to allow efficient transfer of NEDD8 from the E2 to the cullin substrates. Involved in the release of inhibitory effets of CAND1 on cullin-RING ligase E3 complex assembly and activity. Acts also as an oncogene facilitating malignant transformation and carcinogenic progression.
Gene References into Functions
The expression of DCUN1D1 was significantly increased in colorectal cancer with a negative correlation to miR-520b expression in colorectal cancer tissues. PMID: 28470146
DCUN1D1 is a target gene of miR-195 in cervical cancer cells. PMID: 29750306
the DCN1-UBC12 interaction is inhibited by DI-591, a high-affinity, cell-permeable small-molecule inhibitor that binds to purified recombinant human DCN1 and DCN2 proteins with K i values of 10-12 nM PMID: 29074978
SCRO has potential to become a new target for the treatment of PC PMID: 29077169
We also found that both miR-195 and DCUN1D1 siRNAs can inhibit cell invasion possibly through downregulating Matrix metalloproteinase-2 (MMP-2) and Matrix metalloproteinase-9 (MMP-9) at the post-transcriptional level, which can be attenuated by restoring the expression of DCUN1D1 PMID: 28791411
The ubiquitin-associated (UBA) domain of SCCRO/DCUN1D1 protein serves as a feedback regulator of biochemical and oncogenic activity. PMID: 25411243
SCCRO3 functions as a tumor suppressor by antagonizing the neddylation activity of SCCRO PMID: 25349211
Distinct preferences of UBC12 and UBE2F peptides for inhibiting different DCNLs, including the oncogenic DCNL1. PMID: 23201271
substrate engagement prompts DCNL1 recruitment that facilitates the initiation of CUL2 neddylation and define DCNL1 as a "substrate sensor switch" for ECV activation. PMID: 23401859
a mono-ubiquitination-mediated mechanism that governs nuclear-cytoplasmic trafficking of hDCNL1, thereby regulating hDCNL1-dependent activation of the cullin-RING E3 ubiquitin ligases in selected cellular compartments. PMID: 21813641
Loss of SCRO expression in primary adrenocortical carcinoma is associated with worse outcome and may be a marker of progressive dedifferentiation in these tumors. PMID: 15657565
SCCRO regulates Gli1--a key regulator of the hedgehog (HH) pathway. PMID: 17018598
SCCRO recruits Ubc12 approximately NEDD8 to the CAND1-Cul1-ROC1 complex but that this is not sufficient to dissociate or overcome the inhibitory effects of CAND1 on cullin neddylation PMID: 18826954
SCCRO-induced invasion involves activation of MMP2 transcription in an AP2- and p53-dependent manner. PMID: 18980971
The GG genotype of the DCUN1D1 rs4859147 Single Nucleotide Polymorphism represents a risk factor for the development of frontotemporal lobar degeneration , increasing the risk of about fourfold. PMID: 19473369
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Subcellular Location
Nucleus. Cytoplasm.
Tissue Specificity
Expressed in pancreas, kidney, placenta, brain and heart. Weakly or not expressed in liver, skeletal muscle and lung. Strongly overexpressed in thyroid tumors, bronchioloalveolar carcinomas, and malignant tissues of squamous cell carcinoma of the oral ton