1: J Cell Biochem. 2004 May 15;92(2):258-69. 

P53 down-regulates matrix metalloproteinase-1 by targeting the communications
between AP-1 and the basal transcription complex.

Sun Y, Zeng XR, Wenger L, Firestein GS, Cheung HS.

Department of Medicine, University of Miami School of Medicine, Miami, Florida
33101, USA. ysun@med.miami.edu

We have previously reported that human matrix metalloproteinase-1 (MMP1) is a
p53 target gene subject to down-regulation (Sun et al. [1999]: J Biol Chem
274:11535-11540]. In the present study, we demonstrate that the down-regulation
of the human -83MMP1 promoter fragment by p53 was abolished when the -72AP-1
site was eliminated and that a GAL4-cJun-mediated but not a GAL4-Elk1-mediated
induction of pFR-luci was effectively inhibited by p53 suggesting an AP-1
dependent but AP-1 binding independent mechanism. Results from gel mobility
shift assays were consistent with an AP-1 binding independent mechanism. We also
demonstrate that both p300 and TATA box binding proteins cooperated with the
transcription factor AP-1 to induce the promoter of MMP1; however, p53 only
inhibited the p300-mediated induction of the MMP1 promoter and the inhibition
was -72AP-1 dependent. Furthermore, the down-regulation of the MMP1 promoter and
mRNA by p53 could be reversed by p300 and by a p53 binding p300 fragment that
had no coactivator activity. Taken together, these results indicate that p53
down-regulates MMP1 mainly by disrupting the communications between the
transactivator AP-1 and the basal transcriptional complex, which are partially
mediated by p300. Finally, by using p53 truncated mutant constructs, we
demonstrate that both the N-terminal activation domain and the C-terminal
oligomerization domains of p53 were required for the down-regulation of MMP1
transcription. Copyright 2004 Wiley-Liss, Inc.

PMID: 15108353 [PubMed - indexed for MEDLINE]


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2: Eur J Neurosci. 2001 Oct;14(8):1303-12. 

Biological activity of RE-1 silencing transcription factor (REST) towards
distinct transcriptional activators.

Lietz M, Bach K, Thiel G.

Department of Medical Biochemistry and Molecular Biology, University of Saarland
Medical Center, D-66421 Homburg, Germany.

The zinc finger protein RE-1 silencing transcription factor (REST) is a
transcriptional repressor that represses neuronal genes in non-neuronal tissues.
We have analyzed the ability of REST and the REST mutants, RESTDeltaN and
RESTDeltaC lacking either the N-terminal or C-terminal repression domains of
REST, to inhibit transcription mediated by distinct transcriptional activator
proteins. For this purpose we have designed an activator specific assay where
transcription is activated as a result of only one distinct activation domain.
In addition, binding sites for REST were inserted in the 5'-untranslated region
or at a distant position downstream of the polyadenylation signal. The results
show that REST or the REST mutants containing only one repression domain were
able to block transcriptional activation mediated by the transcriptional
activation domains derived from p53, AP2, Egr-1, and GAL4. Moreover, REST, as
well as the REST mutants, blocked the activity of the phosphorylation-dependent
activation domain of Elk1. However, the activity of the activation domain
derived from cAMP response element binding protein 2 (CREB2), was not inhibited
by REST, RESTDeltaN or RESTDeltaC, suggesting that REST is able to distinguish
between distinct transcriptional activation domains. Additionally, the activator
specific assay, together with a positive-dominant mutant of REST that activated
instead of repressed transcription, was used in titration experiments to show
that REST has transcriptional repression and no transcriptional activation
properties when bound to the 5'-untranslated region of a gene.

PMID: 11703459 [PubMed - indexed for MEDLINE]


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