Role of ubiquitin carboxyl terminal hydrolase in the differentiation of human acute lymphoblastic leukemia cell line, Reh

Maki, Auday; Mohammad, Ramzi M.; Smith, Mitchell R.; Al‐Katib, Ayad

doi:10.1046/j.1432-0436.1996.6010059.x

Cited by 16 publications

(5 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Gene expression analyses have identi®ed a number of downstream targets that are induced by TPA, and some of them may be essential for the onset of differentiation. For example, expression of the ubiquitin C-terminal hydrolase gene has been shown to be associated with TPA-induced differentiation of an acute lymphoblastic leukemia cell line, Reh, to a mature non-dividing state (7). Differential regulation of c-myc, c-max and mxi1 expression has also been reported in leukemia cells undergoing TPA-induced differentiation (8).…”

Section: Introductionmentioning

confidence: 99%

Gene expression of TPA induced differentiation in HL-60 cells by DNA microarray analysis

Zheng

Ravatn²,

Lin³

et al. 2002

Nucleic Acids Research

View full text Add to dashboard Cite

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) is a potent inducer of differentiation in human promyelocytic leukemia cells. Recently, TPA has been successfully administered to patients with myelocytic leukemia and has produced therapeutic effects that led to temporary remission. These studies demonstrated the potential efficacy of TPA in cancer chemotherapy. We now seek to understand the biological effects and molecular mechanisms of differentiation in response to TPA treatment in leukemia cells by expression profiling using DNA microarray. Our results show distinct temporal and coordinated gene changes that are consistent with differentiation and activation of multiple biochemical pathways in HL-60 cells exposed to TPA. Alterations of gene expression in HL-60 cells include various transcription factors, cytokines and protein markers that are consistent with the induction of differentiation elicited by TPA. These temporal patterns of gene expression were abolished or greatly diminished in an HL-60 derived TPA- resistant variant cell line (HL-525), thus revealing transcriptional and consequential biochemical changes that may be required for TPA-induced differentiation. In addition, certain genes were upregulated by TPA in TPA-resistant HL-525 cells but not in TPA-sensitive HL-60 cells suggesting that these genes may play a role in the resistant phenotype. These patterns of gene expression may be important for predicting response to TPA.

show abstract

Section: Introductionmentioning

confidence: 99%

Gene expression of TPA induced differentiation in HL-60 cells by DNA microarray analysis

Zheng

Ravatn²,

Lin³

et al. 2002

Nucleic Acids Research

View full text Add to dashboard Cite

show abstract

“…Recently, important biological roles have been discovered for many members of this family. For example, the human Unph gene encodes a deubiquitinating enzyme whose overexpression leads to oncogenic transformation of NIH3T3 cells (10); tre-2 oncogene is structurally related to Unph and also encodes a deubiquitinating enzyme (11); DUBs are a subfamily of cytokine-inducible, immediateearly genes that encode a deubiquitinating enzyme with growth regulatory activities (12); UCH-L1 is involved not only in neural development (13) but also in the differentiation of a lymphoblastic leukemia cell line, Reh (14); and the Drosophilia fat facets gene encodes a deubiquitinating enzyme which is required for eye development in the fly (15).…”

mentioning

confidence: 99%

Kinetic and Mechanistic Studies on the Hydrolysis of Ubiquitin C-Terminal 7-Amido-4-Methylcoumarin by Deubiquitinating Enzymes

1998

View full text Add to dashboard Cite

Deubiquitinating enzymes constitute a family of cysteine hydrolases that specifically cleave ubiquitin-derived substrates of general structure Ub-X, where X can be any number of leaving groups ranging from small thiols and amines to Ub and other proteins (Ub, ubiquitin). We have developed a general assay for deubiquitinating enzymes based on the substrate ubiquitin C-terminal 7-amido-4-methylcoumarin (Ub-AMC). Ub-AMC is efficiently hydrolyzed with liberation of highly fluorescent AMC by two rabbit reticulocyte deubiquitinating enzymes: isopeptidase T (IPaseT), a member of the gene family of ubiquitin-specific processing enzymes, and UCH-L3, a member of the family of ubiquitin C-terminal hydrolases. We used this new assay to probe kinetic and mechanistic aspects of catalysis by IPaseT and UCH-L3. Results from four series of experiments are discussed: (1) For UCH-L3, we determined steady-state kinetic parameters that suggest a diffusion-limited reaction of UCH-L3 with Ub-AMC. To probe this, we determined the viscosity dependence of kc/Km, as well as kc. We found complex viscosity dependencies and interpreted these in the context of a model in which association and acylation are viscosity-dependent but deacylation is viscosity-independent. (2) The kinetics of inhibition of UCH-L3 by ubiquitin C-terminal aldehyde (Ub-H) were determined and reveal a Ki that is less than 10(-14) M. Several mechanisms are considered to account for the extreme inhibition. (3) The IPaseT-catalyzed hydrolysis of Ub-AMC is modulated by Ub with activation at low [Ub] and inhibition at high [Ub]. (4) Finally, we compare kc/Km values for deubiquitinating enzyme-catalyzed hydrolysis of Ub-AMC and Z-Leu-Arg-Gly-Gly-AMC. For IPaseT, the ratio of rate constants is 10(4), while for UCH-L3 this ratio is > 10(7). These results suggest the following: (i) Deubiquitinating enzymes are able to utilize the free energy that is released from remote interactions with Ub-containing substrates for stabilization of catalytic transition states, and (ii) UCHs are more efficient at utilizing the energy from these interactions, presumably because they do not possess a binding domain for a Ub "leaving group".

show abstract

“…Functionally, PGP 9.5 belongs to the ubiquitin C-terminal hydrolase (UCH) family (5), which regulates ubiquitin-mediated proteolysis by cleavage of amide bonds at the C-terminus of ubiquitin (12). It is becoming increasingly clear that these enzymes are a part of the cellular proteolytic pathway that regulates many processes that are essential for various cellular functions, including cellular differentiation (13,14) and cell cycle regulation (15). This multifunctional role of the UCH family in cellular functions suggests that PGP 9.5 expressed in newborn and adult rat kidney contributes to nephrogenesis and the cellular function of PEC.…”

Section: Discussionmentioning

confidence: 99%

Protein Gene Product 9.5 Is Selectively Localized in Parietal Epithelial Cells of Bowman's Capsule in the Rat Kidney

Shirato¹,

Asanuma²,

Takeda³

et al. 2000

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Abstract. Parietal epithelial cells (PEC) of Bowman's capsules cover the inner aspect of Bowman's capsules and are believed to contribute to extracapillary lesions of glomerulonephritis such as crescent formation. In glomerular research including cell culture experiments and pathology, differentiation between PEC and podocytes has frequently been a major problem. Immunohistochemistry of the adult rat kidney for protein gene product 9.5 (PGP 9.5), a neuron-specific ubiquitin C-terminal hydrolase, demonstrated selective localization of the immunoreactivity in PEC. At the urinary pole of the glomerulus, immunoreactive PEC were clearly differentiated from proximal tubular cells that were negative for PGP 9.5. In the subcapsular nephrogenic zone of newborn rat kidney, immunoreactivity was observed in almost all cells in the commashaped body and early S-shaped body and selectively in PEC in the late S-shaped body and capillary-stage glomerulus. In rat glomerular disease models (Masugi-nephritis and puromycin aminonucleoside nephrosis), cells that consisted of cellular crescents or adhered to glomerular tufts were positive for PGP 9.5. The selective localization of PGP 9.5 in PEC in rat kidney provides a new cytochemical marker for identifying the cells. Development expression of the protein suggests that PGP 9.5 is involved in the processes of nephrogenesis of rat kidney.

show abstract

Role of ubiquitin carboxyl terminal hydrolase in the differentiation of human acute lymphoblastic leukemia cell line, Reh

Cited by 16 publications

References 27 publications

Gene expression of TPA induced differentiation in HL-60 cells by DNA microarray analysis

Gene expression of TPA induced differentiation in HL-60 cells by DNA microarray analysis

Kinetic and Mechanistic Studies on the Hydrolysis of Ubiquitin C-Terminal 7-Amido-4-Methylcoumarin by Deubiquitinating Enzymes

Protein Gene Product 9.5 Is Selectively Localized in Parietal Epithelial Cells of Bowman's Capsule in the Rat Kidney

Contact Info

Product

Resources

About