PU.1-dependent Regulation of UCH L1 Expression in B-lymphoma Cells

Overview

Journal Leuk Lymphoma

Specialties Hematology
Oncology

Date 2011 Apr 21

PMID 21504384

Citations 12

Authors

Anjali Bheda

Wei Yue

Anuradha Gullapalli

Julia Shackelford

Joseph S Pagano

Affiliations

Soon will be listed here.

Abstract

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.1 induces UCH L1 expression through direct activation of the uch l1 promoter. Using chromatin immunoprecipitation (ChIP) assays and direct mutagenesis we identified PU.1 binding sites on the uch l1 promoter, at least three of which are involved in this activation. We also show that the viral transcriptional co-activator EBNA2 dramatically increases PU.1-dependent up-regulation of endogenous UCH L1 expression. Finally, inhibition of PU.1 expression with specific shRNA resulted in reduction of UCH L1 mRNA and protein levels in Epstein-Barr virus (EBV)-transformed B-cells. We propose that the ubiquitin-editing enzyme UCH L1 is a multifunctional pro-oncogenic factor involved in development and progression of certain lymphoid malignancies, including EBV-associated lymphomas.

Citing Articles

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The Epstein-Barr virus noncoding RNA EBER2 transactivates the UCHL1 deubiquitinase to accelerate cell growth.

Li Z, Baccianti F, Delecluse S, Tsai M, Shumilov A, Cheng X Proc Natl Acad Sci U S A. 2021; 118(43).

PMID: 34686609 PMC: 8639328. DOI: 10.1073/pnas.2115508118.

Inhibition of UCH-L1 Deubiquitinating Activity with Two Forms of LDN-57444 Has Anti-Invasive Effects in Metastatic Carcinoma Cells.

Kobayashi E, Hwang D, Bheda-Malge A, Whitehurst C, Kabanov A, Kondo S Int J Mol Sci. 2019; 20(15).

PMID: 31370144 PMC: 6696221. DOI: 10.3390/ijms20153733.

C-Terminal Farnesylation of UCH-L1 Plays a Role in Transport of Epstein-Barr Virus Primary Oncoprotein LMP1 to Exosomes.

Kobayashi E, Aga M, Kondo S, Whitehurst C, Yoshizaki T, Pagano J mSphere. 2018; 3(1).

PMID: 29435490 PMC: 5806207. DOI: 10.1128/mSphere.00030-18.

EBF1 binds to EBNA2 and promotes the assembly of EBNA2 chromatin complexes in B cells.

Glaser L, Rieger S, Thumann S, Beer S, Kuklik-Roos C, Martin D PLoS Pathog. 2017; 13(10):e1006664.

PMID: 28968461 PMC: 5638620. DOI: 10.1371/journal.ppat.1006664.

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