Figure 6. UBQLN1 is lost and under-expressed in human cancers.

(a) UBQLN1 is frequently lost and underexpressed in cancer cell lines. Cancer cell lines are separated by UBQLN1 copy number status and their corresponding UBQLN1 expression plotted. Box-plots depict the median group expression (middle line), the 25th and 75th percentiles (bottom and top of box, respectively), with the whiskers indicating the 10th and 90th percentiles. Values for all samples outside this range are represented by dots. The UBQLN1 locus is lost in 243 of the 877 cell lines examined. UBQLN1 is significantly under-expressed in samples with UBQLN1 loss or deletion (p<0.0001, Mann-Whitney U-Test). (b) UBQLN1 is frequently lost and underexpressed in human lung adenocarcinomas. Samples are plotted as in A. The UBQLN1 locus is lost in 117 of 230 lung cancers examined. UBQLN1 is significantly underexpressed in tumors with loss or deletion (p<0.0001, Mann-Whitney U-Test). (c) Cancer relevant nonsense mutations in UBQLN1 are degraded in a proteasome dependent manner. Two nonsense mutations found in UBQLN1 in human cancers (UBQLN1^G573X and UBQLN1^G499X) were introduced into wild-type UBQLN1 (UBQLN1^wt). Constructs expressing the indicated gene or an empty vector (V) were transfected into 293t cells and 36 hours post transfection they were treated with MG132 for the indicated times. GFP is expressed from the same mRNA as the UBQLN1 genes following and IRES. (d) Recurrent mutations observed in both UBQLN1 and UBQLN2 which have been identified in human lung cancers. (e) Loss of UBQLN2 induces EMT. UBQLN2 loss induces EMT in A549 and H358 cells. A549 and H358 cells were transfected with either with non-targeting siRNA (siNT) or siRNAs targeting UBQLN2 (siU2-5, siU2-6). After 72 hrs of transfection cells were harvested and analyzed for protein expression using the indicated antibodies. Arrow indicates the UBQLN2 band.