1: Mol Cell Biol. 2001 Nov;21(21):7391-402. 

Human T-cell lymphotropic virus type 1 Tax represses c-Myb-dependent
transcription through activation of the NF-kappaB pathway and modulation of
coactivator usage.

Nicot C, Mahieux R, Pise-Masison C, Brady J, Gessain A, Yamaoka S, Franchini G.

Section of Animal Models and Retroviral Vaccines, Basic Research Laboratory,
Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892,
USA. cbeden@helix.nih.gov

The proto-oncogene c-myb is essential for a controlled balance between cell
growth and differentiation. Aberrant c-Myb activity has been reported for
numerous human cancers, and enforced c-Myb transcription can transform cells of
lymphoid origin by stimulating cellular proliferation and inhibiting apoptotic
pathways. Here we demonstrate that activation of the NF-kappaB pathway by the
HTLV-1 Tax protein leads to transcriptional inactivation of c-Myb. This
conclusion was supported by the fact that Tax mutants unable to stimulate the
NF-kappaB pathway could not inhibit c-Myb transactivating functions. In
addition, inhibition of Tax-mediated NF-kappaB activation by coexpression of
IkappaBalpha restored c-Myb transcription, and Tax was unable to block c-Myb
transcription in a NEMO knockout cell line. Importantly, physiological stimuli,
such as signaling with the cellular cytokines tumor necrosis factor alpha,
interleukin 1 beta (IL-1beta), and lipopolysaccharide, also inhibited c-Myb
transcription. These results uncover a new link between extracellular signaling
and c-Myb-dependent transcription. The mechanism underlying NF-kappaB-mediated
repression was identified as sequestration of the coactivators CBP/p300 by RelA.
Interestingly, an amino-terminal deletion form of p300 lacking the C/H1 and KIX
domains and unable to bind RelA retained the ability to stimulate c-Myb
transcription and prevented NF-kappaB-mediated repression.

PMID: 11585920 [PubMed - indexed for MEDLINE]


---------------------------------------------------------------


2: Blood. 1998 Jun 1;91(11):4136-44. 

NF-kappaB transcription factors are involved in normal erythropoiesis.

Zhang MY, Sun SC, Bell L, Miller BA.

Department of Pediatrics, Pennsylvania State University College of Medicine,
Milton S. Hershey Medical Center, Hershey, PA 17033-0850, USA.

NF-kappaB/Rel designates a widely distributed family of transcription factors
involved in immune and acute phase responses. Here, the expression and function
of NF-kappaB factors in erythroid proliferation and differentiation were
explored. In an erythroleukemia cell line, TF-1, high levels of p105/p50,
p100/p52, p65, and IkappaBalpha were detected 24 hours after growth factor
deprivation. In response to granulocyte-macrophage colony-stimulating factor
(GM-CSF) stimulation, significant induction of p52 expression was observed.
GM-CSF also induced nuclear translocation of both p52 and p65. No induction of
NF-kappaB factors was observed with erythropoietin stimulation of TF-1 cells.
Overexpression of p52 and p65 in TF-1 cells by transient transfection resulted
in significant induction of a kappaB-TATA-luciferase reporter plasmid, showing
that these factors are functional in vivo in erythroid cells. To determine
whether NF-kappaB factors may play a role in normal erythropoiesis, levels of
these factors were determined in burst-forming unit-erythroid (BFU-E)-derived
cells at different stages of differentiation. The NF-kappaB factors p105/p50,
p100/p52, and p65 were highly expressed in early BFU-E-derived precursors, which
are rapidly proliferating, and declined during maturation. Furthermore, nuclear
levels of NF-kappaB factors p50, p52, and p65 were higher in less mature
precursors (day 10 BFU-E-derived cells) compared with more differentiated (day
14) erythroblasts. In nuclear extracts from day 10 BFU-E-derived cells, p50,
p52, and p65 were able to form complexes, which bound to kappaB sites in the
promoters of both the c-myb and c-myc genes, suggesting that c-myb and c-myc may
be among the kappaB-containing genes regulated by NF-kappaB factors in normal
erythroid cells. Taken together, these data show that NF-kappaB factors are
modulated by GM-CSF and suggest they function to regulate specific kappaB
containing genes involved in erythropoiesis.

PMID: 9596659 [PubMed - indexed for MEDLINE]


---------------------------------------------------------------