UCH-L1 (4p13) (DUB) Ubikiinitioesteraasi 1, neuronin sytoplasminen proteiini 9.5 (PGP9.5)

 Neuronispesifinen ubikitiinin c-terminaalinen hydrolaasi, tuumorisuppressiogeeni

UCHL1, a DUB Regulating p53 Stability and Tumorigenesis

Ubiquitin C-terminal hydrolase L1 (UCHL1), a member of the UCH class of DUBs, is probably the most studied DUB: its association with neurodegenerative conditions, including Parkinson’s disease, and a wide range of malignancies have generated an abundant literature. Despite this, many aspects of the molecular mechanisms and functions of UCHL1 remain either contradictory or poorly understood. While UCHL1 is normally almost exclusively expressed in neurones, the neuroendocrine system and the gonads, its aberrant expression has been described in many tumour types (reviewed in [51]).

While clear roles for UCHL1 in the DDR have not been formally demonstrated, UCHL1 can be included in the list of DUBs that have been reported to modulate the ubiquitylation status of proteins in the p53-mdm2 checkpoint pathways. Thus, in breast cancer models, UCHL1 can induce the levels of p53 and reduce mdm2 protein levels.

UCHL1 also induced G0/G1 cell-cycle arrest and apoptosis of breast tumour cells, an activity that requires its catalytic activity and depends on the accumulation of p53 [140]. Similar observations have also been made in head and neck cancer [141], as well as in prostate cancer [142]. The above mentioned publications all support a role for UCHL1 as a tumour suppressor gene; although it is also important to mention that several reports have demonstrated oncogenic properties for UCHL1 in other cancer types such as lymphoma [143] and colorectal cancer [144]. UCHL1 therefore seems to play important roles in tumorigenesis but a clear understanding of a mechanism for this or for a DDR role(s) remains to be firmly established. It is also quite difficult to reconcile the roles played by UCHL1 in neurons and neuro-endocrine cells, with its functions in cancer cells.

• UCH-LI gene (Pub Med search), 4p13

Also known as

NDGOA; PARK5; PGP95; SPG79; PGP9.5; Uch-L1; HEL-117; PGP 9.5; HEL-S-53

Summary

The protein encoded by this gene belongs to the peptidase C12 family. This enzyme is a thiol protease that hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin. This gene is specifically expressed in the neurons and in cells of the diffuse neuroendocrine system. Mutations in this gene may be associated with Parkinson disease.[provided by RefSeq, Sep 2009]

Expression

Biased expression in brain (RPKM 389.7), adrenal (RPKM 70.8) and 2 other tissues See more

Orthologs

mouse all Related articles in PubMed

Preferred Names

ubiquitin carboxyl-terminal hydrolase isozyme L1

Names

epididymis luminal protein 117

epididymis secretory protein Li 53

neuron cytoplasmic protein 9.5

ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase)

ubiquitin thioesterase L1

ubiquitin thiolesterase

Related articles in PubMed

1. The deubiquitinating enzyme UCHL1 is a favorable prognostic marker in neuroblastoma as it promotes neuronal differentiation. Gu Y, et al. J Exp Clin Cancer Res, 2018 Oct 25. PMID 30359286, Free PMC Article
2. UCHL1/PGP 9.5 Dynamic in Neuro-Immune-Cutaneous Milieu: Focusing on Axonal Nerve Terminals and Epidermal Keratinocytes in Psoriatic Itch. Kupczyk P, et al. Biomed Res Int, 2018. PMID 30148172, Free PMC Article
3. Upregulation of Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCHL1) Mediates the Reversal Effect of Verapamil on Chemo-Resistance to Adriamycin of Hepatocellular Carcinoma. Yang G, et al. Med Sci Monit, 2018 Apr 8. PMID 29627846, Free PMC Article
4. High Expression of Ubiquitin C-terminal Hydrolase L1 Is Associated With Poor Prognosis in Endometrial Cancer Patients. Nakao K, et al. Int J Gynecol Cancer, 2018 May. PMID 29489474
5. Ubiquitin C-Terminal Hydrolase L1 regulates autophagy by inhibiting autophagosome formation through its deubiquitinating enzyme activity. Yan C, et al. Biochem Biophys Res Commun, 2018 Mar 4. PMID 29462615
   

GeneRIFs: Gene References Into Functions

1. high expression is a strong marker of poor prognosis of endometrial cancer
2. these results identified UCHL1 as a target podocyte protein of autoantibodies in a set of relapsing patients and support a causative role of anti-UCHL1 autoantibodies in the development of idiopathic steroid sensitive nephrotic syndrome
3. serum level not significantly elevated in newborns at risk for hypoxic ischemic encephalopathy but with normal EEGs
4. bserved significantly altered density of PGP 9.5-positive axonal nerve terminals in pruritic lesional and nonlesional psoriatic skin compared with controls;PGP 9.5 expression by suprabasal keratinocytes (SBKs) was significantly increased in itchy skin lesions compared to skin without itch.
5. This study demonstrated that UCHL1 expression is induced by HCV infection. UCHL1 stimulates JNK phosphorylation and signaling related to HSCs activation after binding to the cell surface of HSCs.
6. Study showed that UCHL1 could serve as a prognostic marker indicating a favorable clinical outcome in Neuroblastoma (NB). UCHL1 expression was higher in ganglioneuroblastomas/ganglioneuromas (GNB/ GN) and well-differentiated NB than poorly differentiated NB, and UCHL1 expression was strongly associated with differentiation markers, indicating the positive correlation between UCHL1 expression and NB differentiation.
7. The proteins UCH-L1 and alpha-internexin could be independent prognostic biomarkers of pancreatic neuroendocrine tumors.
8. We have also demonstrated that UCHL1 S-nitrosylation provides seeding for faster aggregation of a-synuclein. Finally, the in vitro nitrosylation of UCHL1 was corroborated with rotenone induced mouse model of PD
9. In newborns undergoing cardiac surgery, ubiquitin C-terminal hydrolase 1 showed a significant rise at 0 hours in the deep hypothermic circulatory arrest group compared to baseline. Levels returned to baseline at 12 hours. There was an early rise in UCHL1 at 0 hours in the cardiopulmonary bypass group.
10. Overexpression of UCHL1 genes promoted apoptosis in cells treated with VER+ADM. UCHL1 knockdown using siRNA weakened the effect of ADM+VER, indicating that ADM+VER promotes HCC cell apoptosis and that UCHL1 genes participate in VER-mediated promotion in tumor cell apoptosis.
    

HIV-1 gp120 upregulates the expression of ubiquitin carboxyl-terminal esterase L1 (UCH-L1) in umbilical cord blood mononuclear cells and T-cell lines .

• Peptide encoded by UCH-L1. Peptide sequence 1..223

https://www.ncbi.nlm.nih.gov/protein/NP_004172.2

REFERENCE   1  (residues 1 to 223)
  AUTHORS   Gu Y, Lv F, Xue M, Chen K, Cheng C, Ding X, Jin M, Xu G, Zhang Y,
            Wu Z, Zheng L and Wu Y.
  TITLE     The deubiquitinating enzyme UCHL1 is a favorable prognostic marker
            in neuroblastoma as it promotes neuronal differentiation
  JOURNAL   J. Exp. Clin. Cancer Res. 37 (1), 258 (2018)
REFERENCE   2  (residues 1 to 223)
  AUTHORS   Patil UP, Mally PV and Wachtel EV.
  TITLE     Serum biomarkers of neuronal injury in newborns evaluated for
            selective head cooling: a comparative pilot study
  JOURNAL   J Perinat Med 46 (8), 942-947 (2018)  PUBMED   30070096
  REMARK    GeneRIF: serum level not significantly elevated in newborns at risk
            for hypoxic ischemic encephalopathy but with normal EEGs
REFERENCE   3  (residues 1 to 223)
  AUTHORS   Kupczyk P, Reich A, Gajda M, Holysz M, Wysokinska E, Paprocka M,
            Nevozhay D, Chodaczek G, Jagodzinski PP, Ziolkowski P and
            Szepietowski JC.
  TITLE     UCHL1/PGP 9.5 Dynamic in Neuro-Immune-Cutaneous Milieu: Focusing on
            Axonal Nerve Terminals and Epidermal Keratinocytes in Psoriatic
            Itch
  JOURNAL   Biomed Res Int 2018, 7489316 (2018)
REFERENCE   4  (residues 1 to 223)
  AUTHORS   Lee T, Chikkabyrappa SM, Reformina D, Mastrippolito A, Chakravarti
            SB, Mosca RS, Shaw G and Malhotra SP.
  TITLE     Ubiquitin C-Terminal Hydrolase 1 and Phosphorylated Axonal
            Neurofilament Heavy Chain in Infants Undergoing Cardiac Surgery:
            Preliminary Assessment as Potential Biomarkers of Brain Injury
  JOURNAL   World J Pediatr Congenit Heart Surg 9 (4), 412-418 (2018)
REFERENCE   8  (residues 1 to 223)
  AUTHORS   Edwards YH, Fox MF, Povey S, Hinks LJ, Thompson RJ and Day IN.
  TITLE     The gene for human neurone specific ubiquitin C-terminal hydrolase
            (UCHL1, PGP9.5) maps to chromosome 4p14
  JOURNAL   Ann. Hum. Genet. 55 (4), 273-278 (1991)

Muistiin UCH-L1 deubikitinaasista 
12.5. 2019