UNASSIGNED: Recently, investigators have shown that ubiquitin-proteasome-mediated protein degradation is critical in regulating the balance between bone formation and bone resorption. The major signal transduction pathways regulating bone formation are the RANK/NF-kB pathway and the Wnt/ @entity3546 pathway. These signal transduction pathways regulate the activity of mature osteoblasts and osteoclasts. In addition, The Wnt/ @entity3546 pathway is one of the major signaling pathways in the differentiation of osteoblasts. The ubiquitin ligases that are reported to be of major significance in regulating these pathways are the ubiquitin @entity30200 ) ligase (which regulates activation of NF-kB via degradation of @entity4284 in osteoclasts, and regulates bone transcription factors via degradation of @entity3546 ), the Keap-Cul3-Rbx1 ligase (which regulates degradation of IkB kinase, @entity13791 , and the antiapoptotic factor @entity588 ), and @entity7381 . Also of significance in regulating osteoclastogenesis is the deubiquitinase, @entity1131 ( @entity1131 ), which facilitates the separation of NF-kB from @entity4284 . The degradation of @entity1131 is also under the regulation of @entity30200 ). Proteasome inhibitors influence the activity of mature osteoblasts and osteoclasts, but also modulate the differentiation of precursor cells into osteoblasts. Preclinical studies show that @entity2493 also influences bone metabolism by stimulating bone growth and inhibiting osteoclast activity. These actions of @entity2493 could be interpreted as being mediated by the ubiquitin ligases @entity30200 ) and Keap-Cul3-Rbx, or as an inhibitory effect on proteasomes. Clinical trials of the use of @entity2493 in the treatment of @entity79 , including multiple @entity1582 , using both continuous and intermittent modes of administration, are warranted.

XXXX , bone regulation and the ubiquitin-proteasome connection: A review.

@entity588 :: ('596', 'Gene') :: ['Bcl-2'] @entity1131 :: ('MESH:D011488', 'Disease') :: ['cylindramatosis protein', 'CYLD'] @entity4284 :: ('4792', 'Gene') :: ['IkBa'] @entity3546 :: ('1499', 'Gene') :: ['b-catenin'] @entity2493 :: ('MESH:D008550', 'Chemical') :: ['melatonin'] @entity13791 :: ('4780', 'Gene') :: ['Nrf2'] @entity79 :: ('MESH:D001847', 'Disease') :: ['bone disease'] @entity1582 :: ('MESH:D009101', 'Disease') :: ['myeloma'] @entity30200 :: ('8945', 'Gene') :: ['SCF(B-TrCP'] @entity7381 :: ('57154', 'Gene') :: ['Smurf1']
@entity2493 :: (MESH:D008550,Chemical) :: ['Melatonin']
