Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The region of human chromosome 11p15.5 is linked with Beckwith-Wiedemann syndrome that is associated with susceptibility to Wilms' tumor, rhabdomyosarcoma and hepatoblastoma. TSSC5 (tumor-suppressing subchromosomal transferable fragment cDNA; also known as ORCTL2/IMPT1/BWR1A/SLC22A1L) is located in the region. The expression of TSSC5 and other genes in the region is regulated through paternal imprinting. Mutations and/or reduced expression of TSSC5 have been found in certain tumors. TSSC5 encodes an efflux transporter-like protein with 10 transmembrane domains, whose regulation may affect drug sensitivity, cellular metabolism and growth. Here, we present evidences indicating that RING105, a novel conserved RING-finger protein with a PA (protease-associated) domain and a PEST sequence, is a ubiquitin ligase for TSSC5 that can function in concert with the ubiquitin-conjugating enzyme UbcH6. The polyubiquitin target site on TSSC5 was mapped to a region in the 6th hydrophilic loop. Ectopic expression of RING105 in HeLa cells caused an accumulation of cells during G1 that was not observed with the expression of a form of RING105 in which a residue within the RING finger was mutated to inactivate its ligase activity. UbcH6-RING105 may define a novel ubiquitin-proteasome pathway that targets TSSC5 in mammalian cells.
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PMID:Tumor suppressor candidate TSSC5 is regulated by UbcH6 and a novel ubiquitin ligase RING105. 1631 44

Management of aggressive malignant musculoskeletal tumors is clinically challenging and awaits the identification of regulator(s) that can be therapeutically used to improve patient outcome. Autocrine motility factor (AMF), a secreted cytokine, is known to alter the bone microenvironment by linking to its receptor AMFR (AMF Receptor), leading to tumor progression. It was noted that both the ligand and its receptor belong to the moonlighting family of proteins, as they contribute to intracellular metabolic function such as glycolysis and gluconeogenesis by expressing glucose-6-phosphate isomerase AMF/GPI and higher protein degradation by expressing AMFR/gp78 functioning as ubiquitin ligase activity. Thus, AMF/GPI and AMFR/gp78 contribute to higher metabolic turnover of protein and glucose. Recently, a large-scale cohort study including 23 different histological types of musculoskeletal tumors revealed that patients with osteosarcoma, multiple myeloma, rhabdomyosarcoma, and angiosarcoma tend to express higher levels of AMF, whereas multiple myeloma patients expressed high levels of AMFR. Consistently, the cellular data showed that a variety of musculoskeletal tumors express AMF and components of bone microenvironment express AMFR. Thus, a novel outlook suggests a cellular link and cross-talk between musculoskeletal tumors and the skeletal milieu are regulated by AMF-AMFR signaling. This review will highlight the pharmacological need for AMF and AMFR inhibitors as unmet medical needs for patients with malignant musculoskeletal tumors.
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PMID:Autocrine motility factor and its receptor expression in musculoskeletal tumors. 3310 87