Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transcription factor c-Maf is extensively involved in the pathophysiology of multiple myeloma (MM), a fatal malignancy of plasma cells. In the present study, affinity chromatography and mass spectrometry were used to identify c-Maf ubiquitination-associated proteins, from which the E3 ligase HERC4 was found to interact with c-Maf and catalyzed its polyubiquitination and subsequent proteasome-mediated degradation. HERC4 mediated polyubiquitination at K85 and K297 in c-Maf, and this polyubiquitination could be prevented by the isopeptidase USP5. Further analysis on the NCI-60 cell line collection revealed that RPMI 8226, a MM-derived cell line, expressed the lowest level of HERC4. Primary bone marrow analysis revealed HERC4 expression was high in normal bone marrow, but was steadily decreased during myelomagenesis. These findings suggested HERC4 played an important role in MM progression. Moreover, ectopic HERC4 expression decreased MM proliferation in vitro, and delayed xenograft tumor growth in vivo. Therefore, modulation of c-Maf ubiquitination by targeting HERC4 may represent a new therapeutic modality for MM.
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PMID:The ubiquitin ligase HERC4 mediates c-Maf ubiquitination and delays the growth of multiple myeloma xenografts in nude mice. 2682 10

Recently, more and more evidences unveiled that ubiquitin-proteasome system (UPS) makes an important contribution to the occurrence and development of cancer. HERC4 is one identified Ubiqutin ligase E3, a member of UPS. Although some studies showed that HERC4 abnormally expresses in many cancer cells, till now, nothing has been reported about the function of HERC4 in the development of hepatoma carcinoma. To this end, in this study, we studied the function of HERC4 for the first time in hepatoma carcinoma cells. We detected the expression of HERC4 in tumor and normal tissues, and in hepatoma carcinoma cell lines by using qRT-PCR, Western blot, immunohistochemistry, and immunofluorescence. The data showed that tumor tissues expressed higher HERC4 than normal ones. HERC4 was expressed, although to a different extent, in hepatoma carcinoma cell lines. Colony formation assay, CCK-8 assay, EdU assay, wound healing assay, and FACS indicated that HERC4 plays a role in cell proliferative and migration ability. HERC4 overexpression increases the proliferative and migration ability and reduces apoptosis of hepatoma carcinoma cells; in contrast, knockdown of HERC4 decreases the proliferative and migration ability and increases the apoptosis rate of hepatoma carcinoma cells. Taken together, our findings showed that HERC4 has an effect on the occurrence and development of hepatoma carcinoma by promoting hepatoma carcinoma cell proliferation and migration, and by reducing cell apoptosis, further providing another therapeutic target for the intervention of related diseases.
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PMID:HERC4 Is Overexpressed in Hepatocellular Carcinoma and Contributes to the Proliferation and Migration of Hepatocellular Carcinoma Cells. 2843 May 27