Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ASIC4 is a member of the acid-sensing ion channel family that is broadly expressed in the mammalian nervous system, but has no known function. We demonstrate here that transfected ASIC4 is targeted to the plasma membrane in CHO-K1 cells, where it associates with ASIC1a and downregulates exogenous ASIC1a expression. This effect could also be observed on endogenous H+-gated currents in TSA-201 cells and ASIC3 currents in CHO-K1 cells, suggesting a physiological role for ASIC4 in regulating ASIC currents involved in pain mechanisms. Using a yeast two-hybrid assay we found that ASICs interact with proteins involved in diverse functions, including cytoskeletal proteins, enzymes, regulators of endocytosis and G-protein-coupled pathways. ASIC4 is the sole member of this ion channel class to interact strongly with polyubiquitin. The distinct functionally related sets of interacting proteins that bind individual ASICs identified in the yeast two-hybrid screen suggest potential roles for ASICs in a variety of cellular functions.
 ...
PMID:Regulation of ASIC activity by ASIC4--new insights into ASIC channel function revealed by a yeast two-hybrid assay. 1866 36

Cervical cancer cells exhibit an increased requirement for ubiquitin-dependent protein degradation associated with an elevated metabolic turnover rate. Ubiquitin, which is a small, highly conserved protein expressed in all eukaryotic cells, can be covalently linked to certain target proteins to mark them for degradation by the ubiquitin-proteasome system. Previous studies highlight the essential role of Ubiquitin B (UbB) and UbB-dependent proteasomal protein degradation in histone deacetylase inhibitor (HDACi) -induced tumor selectivity. We hypothesized that UbB plays a critical role in the function of cervical cancer stem cells. We measured endogenous UbB levels in mammospheres in vitro by real-time PCR and Western blotting. The function of UbB in cancer stem-like cells was assessed after knockdown of UbB expression in prolonged Trichostatin A-selected HeLa cells (HeLa/TSA) by measuring in vitro cell proliferation, cell apoptosis, invasion, and chemotherapy resistance as well as by measuring in vivo growth in an orthotopic model of cervical cancer. We also assessed the cancer stem cell frequency, tumorsphere formation, and in vivo growth of human cervical cancer xenografts after UbB silencing. We found that HeLa/TSA were resistant to chemotherapy, highly expressed the UbB gene and the stem cell markers Sox2, Oct4 and Nanog. These cells also displayed induced differentiation abilities, including enhanced migration/invasion/malignancy capabilities in vitro and in vivo. Furthermore, an elevated expression of UbB was shown in the tumor samples of chemotherapy patients. Silencing of UbB inhibited tumorsphere formation, lowered the expression of stem cell markers and decreased cervical xenograft growth. Our results demonstrate that UbB was significantly increased in prolonged Trichostatin A-selected HeLa cells and it played a key role in the maintenance of cervical cancer stem-like cells.
...
PMID:Ubiquitin B in cervical cancer: critical for the maintenance of cancer stem-like cell characters. 2701 54