Therefore UCH-L1 is responsible for conserving the cellular pool of ubiquitin and it has also been implicated in cellular pathways STA-9090 such as proliferation, apoptosis and cell migration . A unique characteristic of UCH-L1 is its ability to act as an ubiquitin ligase in dimeric form, in contrast to acting as a hydrolase in its monomeric form . UCHL-1 is highly Selleckchem KU57788 expressed in the central and
peripheral nervous system, reproductive tissue and neuroendocrine (NE) cells, although it is expressed in most adult tissues [9, 10]. In both reproductive organs and nervous tissue, UCH-L1 promotes apoptosis. In testicular germ cells UCH-L1 expression is responsible for an early apoptotic wave during spermatogenesis but tight MAPK inhibitor regulation of UCH-L1 is important as high levels cause excessive apoptosis in the ovaries and testes of transgenic mice [5, 11]. In retinal neurons the regulation of intracellular ubiquitin by UCH-L1 alters the stability of pro-apoptotic and anti-apoptotic proteins with a substantial increase in Bcl-2 and XIAP levels in UCH-L1 null mice compared to UCH-L1 wildtype [12, 13]. Aberrant
UCH-L1 function in neurons manifests as neurological diseases, such as Parkinson’s disease (PD), where dysfunctions of the ubiquitin-proteasome system allow the accumulation of α-synuclein, which O-methylated flavonoid is important in the pathology of the disease. Mutations
in UCH-L1 have been detected in cases of familial PD. In particular the I93 M amino-acid substitution has been linked to a rare inherited form of PD known as PARK5 [5, 14], whereas the S18Y polymorphism reduces susceptibility to PD . In cancer, UCH-L1 exhibits highly variable expression patterns seemingly in a tumor-specific manner. UCH-L1 can act as a tumor-suppressor and is silenced in ovarian , hepatocellular [9, 17], renal cell [17, 18], head and neck  and oesophageal carcinomas , when compared to normal tissue. The silencing in many cases is due to hypermethylation of the UCH-L1 promoter region [16, 20–22]. On the contrary, UCH-L1 is over-expressed in neuroblastoma , lung carcinoma, independent of neuronal differentiation , myeloma , prostate carcinoma , osteosarcoma  and pancreatic carcinoma . Several types of cancer present contradictory results in relation to UCH-L1 expression patterns and this is the case in both colorectal and breast carcinoma [16, 29–31]. In non-small cell lung carcinoma (NSCLC) UCH-L1 is consistently highly expressed in both cell lines and primary tumour samples when compared to normal lung tissue where the expression of UCH-L1 is confined solely to cells of the neuroendocrine (NE) system.