| Gene Name | UCHL1 |
| HF Protein Name | Ubiquitin carboxyl-terminal hydrolase isozyme L1 |
| HF Function | UCHL1 is a negative regulator of PRR-induced immune responses |
| Uniprot ID | P09936 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 7345 |
| Host Factor (HF) Name in Paper | UCHL1 |
| Gene synonyms | N.A. |
| Ensemble Gene ID | ENSG00000154277 |
| Ensemble Transcript | ENST00000284440;ENST00000503431 |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0002931, GO:0004197, GO:0004843, GO:0005654, GO:0005737, GO:0005789, GO:0005829, GO:0007412, GO:0007628, GO:0008242, GO:0008283, GO:0016241, GO:0016579, GO:0016874, GO:0019233, GO:0019896, GO:0031625, GO:0031694, GO:0036459, GO:0042755, GO:0043025, GO:0043130, GO:0043161, GO:0043209, GO:0043407, GO:0044306, GO:0048747, GO:0050905, GO:0070062, GO:1904115, |
| MINT ID | P09936 |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | 191342 |
| PANTHER ID | PTHR10589;PTHR10589:SF19 |
| PDB ID(s) | 2ETL, 2LEN, 3IFW, 3IRT, 3KVF, 3KW5, 4DM9, 4JKJ, |
| pfam ID | PF01088, |
| Drug Bank ID | N.A., |
| ChEMBL ID | CHEMBL6159 |
| Organism | Homo sapiens (Human) |
| Virus Name | Human papillomavirus type 16 |
| Virus Short Name | HPV16 |
| Order | Unassigned |
| Virus Family | Papillomaviridae |
| Virus Subfamily | N.A. |
| Genus | Alphapapillomavirus |
| Species | Human papillomavirus 16 |
| Host | Human, monkeys |
| Cell Tropism | Epithelial cells of skin, mucous membranes |
| Associated Disease | Malignant tumours |
| Mode of Transmission | Sexual, indirect and direct contact, auto-inoculation |
| VIPR DB link | N.A. |
| ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/dsdna-viruses-2011/w/dsdna_viruses/121/papillomaviridae |
| Virus Host DB link | http://www.genome.jp/virushostdb/view/?virus_lineage=Papillomaviridae |
| Paper Title | Human papillomavirus (HPV) upregulates the cellular deubiquitinase UCHL1 to suppress the keratinocyte's innate immune response |
| Author's Name | Rezaul Karim, Bart Tummers, Craig Meyers, Jennifer L. Biryukov, Samina Alam, Claude Backendorf, Veena Jha, Rienk Offringa, Gert-Jan B. van Ommen, Cornelis J. M. Melief, Daniele Guardavaccaro, Judith M. Boer, Sjoerd H. van der Burg |
| Journal Name | PLOS Pathogens |
| Pubmed ID | 23717208 |
| Abstract | Persistent infection of basal keratinocytes with high-risk human papillomavirus (hrHPV) may cause cancer. Keratinocytes are equipped with different pattern recognition receptors (PRRs) but hrHPV has developed ways to dampen their signals resulting in minimal inflammation and evasion of host immunity for sustained periods of time. To understand the mechanisms underlying hrHPVs capacity to evade immunity, we studied PRR signaling in non, newly, and persistently hrHPV-infected keratinocytes. We found that active infection with hrHPV hampered the relay of signals downstream of the PRRs to the nucleus, thereby affecting the production of type-I interferon and pro-inflammatory cytokines and chemokines. This suppression was shown to depend on hrHPV-induced expression of the cellular protein ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) in keratinocytes. UCHL1 accomplished this by inhibiting tumor necrosis factor receptor-associated factor 3 (TRAF3) K63 poly-ubiquitination which lead to lower levels of TRAF3 bound to TANK-binding kinase 1 and a reduced phosphorylation of interferon regulatory factor 3. Furthermore, UCHL1 mediated the degradation of the NF-kappa-B essential modulator with as result the suppression of p65 phosphorylation and canonical NF-κB signaling. We conclude that hrHPV exploits the cellular protein UCHL1 to evade host innate immunity by suppressing PRR-induced keratinocyte-mediated production of interferons, cytokines and chemokines, which normally results in the attraction and activation of an adaptive immune response. This identifies UCHL1 as a negative regulator of PRR-induced immune responses and consequently its virus-increased expression as a strategy for hrHPV to persist. |
| Used Model | HEK293T cells |
| DOI | 10.1371/journal.ppat.1003384 |
