Expression of protein gene product 9·5 (PGP9·5)/ubiquitin‐C‐terminal hydrolase 1 (UCHL‐1) in human myeloma cells

Abstract

Summary The neuron cytoplasmic protein gene product 9·5 (PGP9·5)/ubiquitin‐C‐terminal hydrolase 1 (UCHL‐1) protein is a thiol protease that recognizes and hydrolyzes a peptide bond at the C‐terminal of ubiquitin, and is involved in the processing of ubiquitin precursors and ubiquinated proteins. Although this molecule is known as a specific tissue marker for the neuroendocrine system, many reports have indicated that PGP9·5 is a marker for certain tumour types, such as cancer of the lung, colon, and pancreas. The expression of PGP9·5 in myeloma cells was examined. PGP9·5 seemed to be expressed specifically in myeloma cells as compared with other haematological malignant cells. In addition, in myeloma cells subjected to growth‐factor starvation, the upregulation of PGP9·5 was observed in association with that of p27Kip1, a cyclin‐dependent‐kinase inhibitor, although the upregulation caused by irradiation was milder. In contrast, the hypoxic culture of myeloma cells induced down‐regulation of PGP9·5. These results suggested that PGP9·5 may be a good marker for myeloma among haematological malignancies. In addition, it may indicate certain cellular features of myeloma cells, such as sensitivity to proteasome inhibitors.

Hypomethylation of the protein gene product 9.5 promoter region in gallbladder cancer and its relationship with clinicopathological features

“…as the cause of transformation. (19)(20)(21)(22)(23)(24)(25)(26)(27) Although PGP9.5 is known to be a dual function protein, that is, as a hydrolase to generate free ubiquitin and as a ligase to produce multi-ubiquitin chains, (17,41) both activities are involved in regulating ubiquitin levels. Moreover, the accumulation of ubiquitin has been documented in various types of primary cancers.…”

“…medullary thyroid carcinoma, (24) ESCC, (25) myeloma (26) and neuroblastoma. (27) Interestingly, a previous methylation analysis of the promoter region of PGP9.5 showed that a virtual absence of methylated CpG sites in lung cancer cell lines is consistent with relatively high PGP9.5 expression, and that dense methylation contributes to the lack of its expression in HeLa cells, (28) suggesting that PGP9.5 expression is regulated by promoter methylation.…”

Involvement of IL-10 and Bcl-2 in resistance against an asbestos-induced apoptosis of T cells

“…Whole cell lysates from drug-treated MT-2 cells were made with lysis buffer (50 mM Tris-HCl (pH 7.2), 150 mM NaCl, 1% Nonidet P-40, 1% deoxycholate and 0.05% SDS) supplemented with protease inhibitor (Sigma-Aldrich Japan Inc., Tokyo, Japan,) as reported previously [21,22]. Soluble fractions were boiled in 1 × SDS loading buffer before electrophoresis.…”

Ubiquitin Hydrolase UCH-L1 Destabilizes mTOR Complex 1 by Antagonizing DDB1-CUL4-Mediated Ubiquitination of Raptor

“…Deletion of Uchl1 in mice leads to a fatal neurodegenerative disorder known as gracile axonal dystrophy (4), and mutations have been identified that impact the pathogenesis of Parkinson's disease (5,6). Expression outside neuroendocrine tissues is found in various cancers, including B cell lymphoma (7), multiple myeloma (2,8), and lung cancer (9). Using transgenic (Tg) mice, we demonstrated that UCH-L1 is in fact an oncogene that causes the same malignancies, most likely by boosting Akt signaling (2).…”