Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.3.2.19 (ubiquitin-protein ligase)
 799 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genetic alterations of RING finger genes, encoding an ubiquitin-protein ligase, are implicated in several types of human cancer through dysregulation of growth regulators. Here, a novel RING finger gene, RNF26, was cloned and characterized. The RNF26 gene on human chromosome 11q23 region was found to encode a polypeptide of 433 amino acids with the N-terminal leucine zipper domain and the C-terminal RING finger domain. Among the RING finger protein family, RING finger domains of RNF26, CGR19, NEURL, KIAA0554, and AK022937 were found to constitute a novel C3HC5 subfamily, which is distinct from C3H2C3 or C3HC4 subfamilies. RING finger domain of RNF26 was most homologous to that of CGR19 (49% amino-acid identity). The 3.2-kb RNF26 mRNA was expressed ubiquitously in normal human tissues, but was upregulated in several human cancer cell lines, including HL-60 (promyelocytic leukemia), HeLa S3 (cervical uterus cancer), SW480 (colorectal cancer), and MKN7 (gastric cancer). In addition, RNF26 was upregulated in 50% of primary gastric cancer examined in this study. Although substrates of ubiquitination mediated by RNF26 remain to be elucidated, RNF26 upregulation in several types of human cancer might be implicated in carcinogenesis through dysregulation of its substrates.
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PMID:Molecular cloning and characterization of RNF26 on human chromosome 11q23 region, encoding a novel RING finger protein with leucine zipper. 1135 57

Human T-cell leukemia virus type 1 (HTLV-1) encodes a protein derived from the antisense strand of the proviral genome designated HBZ (HTLV-1 basic leucine zipper factor). HBZ is the only viral gene consistently expressed in infected patients and adult T-cell leukemia/lymphoma (ATL) tumor cell lines. It functions to antagonize many activities of the Tax viral transcriptional activator, suppresses apoptosis, and supports proliferation of ATL cells. Factors that regulate the stability of HBZ are thus important to the pathophysiology of ATL development. Using affinity-tagged protein and shotgun proteomics, we identified UBR5 as a novel HBZ-binding partner. UBR5 is an E3 ubiquitin-protein ligase that functions as a key regulator of the ubiquitin proteasome system in both cancer and developmental biology. Herein, we investigated the role of UBR5 in HTLV-1-mediated T-cell transformation and leukemia/lymphoma development. The UBR5/HBZ interaction was verified in vivo using over-expression constructs, as well as endogenously in T-cells. shRNA-mediated knockdown of UBR5 enhanced HBZ steady-state levels by stabilizing the HBZ protein. Interestingly, the related HTLV-2 antisense-derived protein, APH-2, also interacted with UBR5 in vivo. However, knockdown of UBR5 did not affect APH-2 protein stability. Co-immunoprecipitation assays identified ubiquitination of HBZ and knockdown of UBR5 resulted in a decrease in HBZ ubiquitination. MS/MS analysis identified seven ubiquitinated lysines in HBZ. Interestingly, UBR5 expression was upregulated in established T lymphocytic leukemia/lymphoma cell lines and the later stage of T-cell transformation in vitro. Finally, we demonstrated loss of UBR5 decreased cellular proliferation in transformed T-cell lines. Overall, our study provides evidence for UBR5 as a host cell E3 ubiquitin-protein ligase responsible for regulating HBZ protein stability. Additionally, our data suggests UBR5 plays an important role in maintaining the proliferative phenotype of transformed T-cell lines.
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PMID:Stability of the HTLV-1 Antisense-Derived Protein, HBZ, Is Regulated by the E3 Ubiquitin-Protein Ligase, UBR5. 2944 Oct 57