Histone acetyltransferase p300 is a coactivator for transcription factor
REL and is C-terminally truncated in the human diffuse large B-cell
lymphoma cell line RC-K8
Michael R. Garbati, Gökçen Alço, Thomas D. Gilmore
*
Department of Biology, Boston University, Boston, MA 02215, USA
article info
Article history:
Received 13 August 2009
Received in revised form 22 October 2009
Accepted 26 October 2009
Keywords:
c-Rel
p300
CBP
RC-K8
Diffuse large B-cell lymphoma
abstract
Human c-Rel (REL) is a member of the NF-
j
B family of transcription factors. REL’s normal
physiological role is in the regulation of B-cell proliferation and survival. The REL gene is
amplified in many human B-cell lymphomas and overexpression of REL can transform
chicken lymphoid cells. In this report, histone acetyltransferase p300 enhanced REL-
induced transactivation and interacted with REL both in vitro and in REL-transformed
chicken spleen cells and the B-lymphoma cell line RC-K8, in which REL is constitutively
active and required for proliferation. However, due to a deletion in the EP300 locus, only
a C-terminally truncated form of p300 is expressed in RC-K8 cells. These results suggest
a role for p300 in REL-mediated oncogenic activity in B lymphoma.
Ó 2009 Elsevier Ireland Ltd. All rights reserved.
1. Introduction
The human c-rel proto-oncogene (REL) encodes a tran-
scription factor in the NF-
j
B family of proteins. Expression
of c-rel is important for normal and malignant B-cell prolif-
eration and survival [1].c-rel knockout mice have immune
deficiencies because their B cells do not proliferate in re-
sponse to mitogenic stimulation [2], and misregulation of
REL has been implicated in B-cell malignancy in several
ways. The REL gene is amplified or mutated in some
types of B-cell lymphoma, including diffuse large B-cell
lymphoma (DLBCL), follicular lymphoma, and Hodgkin’s
lymphoma [1,3]. Overexpression of REL can transform
chicken lymphoid cells [4]. Additionally, REL is constitu-
tively active in many B-lymphoma cell lines, including
the human DLBCL cell line RC-K8 [5].
The REL protein contains a conserved N-terminal DNA-
binding/dimerization domain of approximately 300 amino
acids (aa) called the Rel homology domain (RHD). The C-
terminal half of REL (aa 296–587) contains a transactiva-
tion domain (TAD) with two subdomains: TAD1 consists
of aa 422–497 and TAD2 aa 518–587 [6,7]. Deletion of
the entire C-terminal TAD in mice abolishes the ability of
c-Rel to perform its normal functions in the B-cell immune
response [8]. Moreover, the transforming activity of REL re-
quires at least one of its two TAD subdomains to be present
[7]. Therefore, understanding the mechanism by which REL
activates transcription will help elucidate REL’s normal and
oncogenic activities.
The related histone acetyltransferases CBP and p300 can
act as coactivators for many transcription factors [9,10].
Several groups have shown that CBP/p300 can interact
with NF-
j
B transcription factor RelA to enhance its
0304-3835/$ - see front matter Ó 2009 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.canlet.2009.10.018
Abbreviations: aa, amino acid(s); DLBCL, diffuse large B-cell lym-
phoma; FLAG, flu antigen; NLS, nuclear localization signal; NRG, non-REL
gene; RHD, Rel homology domain; qPCR, quantitative polymerase chain
reaction; RT-PCR, reverse transcriptase-PCR; TAD, transactivation
domain.
* Corresponding author. Address: Biology Department, Boston Univer-
sity, 5 Cummington Street, Boston, MA 02215, USA. Tel.: +1 617 353 5444;
fax: +1 617 353 6340.
E-mail address: gilmore@bu.edu (T.D. Gilmore).
Cancer Letters 291 (2010) 237–245
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Cancer Letters
journal homepage: www.elsevier.com/locate/canlet