PU.1-dependent regulation of UCH L1 expression in B-lymphoma cells.

Elevated levels of ubiquitin C-terminal hydrolase L1 (UCH L1) have been detected in a variety of malignancies, and recent studies show the oncogenic capacity of overexpressed UCH L1 in vivo in animal models. Here we demonstrate that expression of endogenous UCH L1 is significantly higher in B-lymphoma cells than in transformed cells of epithelial and fibroblastic origin. The specific hematopoietic transcription factor PU.

Ubiquitin editing enzyme UCH L1 and microtubule dynamics: implication in mitosis.

Microtubules are essential components of the cytoskeleton and are involved in many aspects of cell responses including cell division, migration, and intracellular signal transduction. Among other factors, post-translational modifications play a significant role in the regulation of microtubule dynamics. Here, we demonstrate that the ubiquitin-editing enzyme UCH L1, abundant expression of which is normally restricted to brain tissue, is also a part of the microtubule network in a variety of transformed cells.

Expression and functional studies of ubiquitin C-terminal hydrolase L1 regulated genes.

Deubiquitinating enzymes (DUBs) have been increasingly implicated in regulation of cellular processes, but a functional role for Ubiquitin C-terminal Hydrolases (UCHs), which has been largely relegated to processing of small ubiquitinated peptides, remains unexplored. One member of the UCH family, UCH L1, is expressed in a number of malignancies suggesting that this DUB might be involved in oncogenic processes, and increased expression and activity of UCH L1 have been detected in EBV-immortalized cell lines. Here we present an analysis of genes regulated by UCH L1 shown by microarray profiles obtained from cells in which expression of the gene was inhibited by RNAi.

Positive reciprocal regulation of ubiquitin C-terminal hydrolase L1 and beta-catenin/TCF signaling.

Deubiquitinating enzymes (DUBs) are involved in the regulation of distinct critical cellular processes. Ubiquitin C-terminal Hydrolase L1 (UCH L1) has been linked to several neurological diseases as well as human cancer, but the physiological targets and the regulation of UCH L1 expression in vivo have been largely unexplored. Here we demonstrate that UCH L1 up-regulates beta-catenin/TCF signaling: UCH L1 forms endogenous complexes with beta-catenin, stabilizes it and up-regulates beta-catenin/TCF-dependent transcription.

Loss of p53 induces epidermal growth factor receptor promoter activity in normal human keratinocytes.

Overexpression of the epidermal growth factor receptor (EGFR) in human papillomavirus type 16-immortalized human keratinocytes (HKc) is caused by the viral oncoprotein E6, which targets p53 for degradation. We have previously observed that expression of p53 RNAi in normal HKc is associated with an increase in EGFR mRNA and protein. We now report that p53 RNAi induces EGFR promoter activity up to approximately 10-fold in normal HKc, and this effect does not require intact p53 binding sites on the EGFR promoter.