Bryostatin 1 induces ubiquitin COOH-Terminal hydrolase in acute lymphoblastic leukemia cells

Ramzi M. Mohammad, Auday Maki, George Pettit, Ayad M. Al-Katib

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

It has been previously reported that Bryostatin 1 (Bryo1) induces differentiation of the human acute lymphoblastic leukemia (ALL) cell line, Reh, to a monocytoid B-cell stage. In this study we demonstrate that a novel protein, ubiquitin COOH-terminal hydrolase (UCH-L1), is associated with this differentiation. Reh cells were treated with 200 nmol/l of Bryo1 for 72 h and analyzed for changes in morphology, surface immunophenotype, acid phosphatase and terminal deoxynucleotidyl transferase. Protein patterns of the parent and differentiated cells, by two-dimensional polyacrylamide gel electrophoresis (2D PAGE), were studied. Bryo1-treated cells expressed morphologic, phenotypic and enzymatic features of the monocytoid B-cell stage. The UCH-L1 enzyme (MW-pI 34-5.3) was detected by 2D PAGE in the differentiated, but not in parent cells. The presence of UCH-L1 in the Bryo1-treated cells was further confirmed by immunoblotting of 2D PAGE using UCH-L1 polyclonal antibody. Ubiquitin expression was studied in parent and Bryo1-treated calls and was compared with 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated cells. Both agents, TPA and Bryo1, increased the level of ubiquitin expression as detected by flow cytometry. Sodium borohydride, an inhibitor of UCH-L1, inhibited the Bryo1-induced differentiating effect on Reh cells. To date, the mechanism by which Bryo1, exerts its B-cell differentiating effect is not fully understood. This study shows that UCH-L1 expression may play a major role in Bryo1-induced differentiation in pre-B-ALL.

Original languageEnglish (US)
Pages (from-to)262-272
Number of pages11
JournalEnzyme and Protein
Volume49
Issue number5-6
DOIs
StatePublished - Jan 1 1996

Keywords

  • Acute lymphoblastic leukemia
  • B Cells
  • Bryostatin 1
  • Differentiation
  • Ubiquitin
  • Ubiquitin COOH-terminal hydrolase

ASJC Scopus subject areas

  • Biochemistry

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