Expression of Deubiquitinating Enzymes in Lung Cancer Cells with Different REST Status

The aims of this study were: (1) to screen a panel of lung cell lines for expression of the proteins UCHL1, USP49, USP15, USP4, and USP11. (2) To investigate the correlation of transcript and protein expression level of these DUBs. (3) To find any proteins that discriminate non-small cell lung cancer (NSCLC) from neuroendocrine (NE) SCLC or benign lung carcinoid. (4) To investigate any correlation of DUB proteins expression with lung cancer sub-types that has different amounts of REST protein. Method: Western blots were performed to detect the expression of DUB expression (USP4, USP11, USP15, USP49, and UCHL1) and REST protein in extracts from normal lung cell lines, SCLC, carcinoid, and NSCLC Results: we found that the transcript level was in general not a good indicator of DUB protein level. There was a significant positive correlation of REST with DUB proteins from whole-cell extracts for USP15, USP11, USP4, and USP49 in normal lung cell lines. The P values were 0.016, 0.002, 0 .018 and 0 .034 respectively. Also in both normal and NSCLC cell lines total USP15, USP11 and USP49 showed a positive correlation with REST. P values were 0.007, 0.029 and 0.001 respectively. However USP11 protein was highly abundant in REST-deficient SCLC. In contrast, both USP11 and USP15 showed a positive correlation with REST in SCLC and NSCLC nuclear extracts. P values were 0.001 and 0.005 respectively. A positive correlation of DUBs with REST would be consistent with their putative role in stabilizing REST.