1: Vet Immunol Immunopathol. 2005 Oct 6; [Epub ahead of print] 

Characterization and expression analysis of TNF-related apoptosis inducing
ligand (TRAIL) in grass carp Ctenopharyngodon idella.

Chang MX, Nie P, Xie HX, Wang GL, Gao Y.

State Key Laboratory of Freshwater Ecology and Biotechnology, and Laboratory of
Fish Diseases, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan,
Hubei Province 430072, PR China.

TRAIL (Apo2 ligand) described as a type II transmembrane protein belonging to
the TNF superfamily can induce apoptotic cell death in a variety of cell types.
In the present study, a putative cDNA sequence encoding the 299 amino acids of
TRAIL (GC-TRAIL) and its genomic organization were identified in grass carp
Ctenopharyngodon idella. The predicted GC-TRAIL sequence showed 44 and 41%
identities to chicken and human TRAILs, respectively. In a domain search, a
tumor necrosis factor homology domain (THD) was identified in the C-terminal
portion of TRAILs. The GC-TRAIL gene consists of five exons, with four
intervening introns, spaced over approximately 4kb of genomic sequence. Analysis
of GC-TRAIL promoter region revealed the presence of a number of putative
transcription factor binding sites, such as Sp1, NF-kappaB, AP-1, GATA, NFAT,
HNF, STAT, P53 and IRF1 sequences which are important for the expression of
other TNF family members. Phylogenetic analysis placed GC-TRAIL and the putative
zebrafish (Danio rerio) TRAIL obtained from searching the zebrafish database
into one separate cluster near mammalian TRAIL genes, but apart from the
reported zebrafish TRAIL-like protein, indicating that the GC-TRAIL is an
authentic fish TRAIL. Expression analysis revealed that GC-TRAIL is expressed in
many tissues, such as in gills, liver, trunk kidney, head kidney, intestine and
spleen.

PMID: 16216337 [PubMed - as supplied by publisher]


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2: J Biol Chem. 2003 Jul 18;278(29):26589-96. Epub 2003 May 5. 

The tumor suppressor interferon regulatory factor 1 interferes with SP1
activation to repress the human CDK2 promoter.

Xie RL, Gupta S, Miele A, Shiffman D, Stein JL, Stein GS, van Wijnen AJ.

Department of Cell Biology, University of Massachusetts Medical School,
Worcester, Massachusetts 01655, USA.

Cell growth control by interferons (IFNs) involves up-regulation of the tumor
suppressor interferon regulatory factor 1 (IRF1). To exert its
anti-proliferative effects, this factor must ultimately control transcription of
several key genes that regulate cell cycle progression. Here we show that the
G1/S phase-related cyclin-dependent kinase 2 (CDK2) gene is a novel
proliferation-related downstream target of IRF1. We find that IRF1, but not
IRF2, IRF3, or IRF7, selectively represses CDK2 gene transcription in a dose-
and time-dependent manner. We delineate the IRF1-responsive repressor element
between nt -68 to -31 of the CDK2 promoter. For comparison, the tumor suppressor
p53 represses CDK2 promoter activity independently of IRF1 through sequences
upstream of nt -68, and the CDP/cut/Cux1 homeodomain protein represses
transcription down-stream of -31. Thus, IRF1 repression represents one of three
distinct mechanisms to attenuate CDK2 levels. The -68/-31 segment lacks a
canonical IRF responsive element but contains a single SP1 binding site.
Mutation of this element abrogates SP1-dependent enhancement of CDK2 promoter
activity as expected but also abolishes IRF1-mediated repression. Forced
elevation of SP1 levels increases endogenous CDK2 levels, whereas IRF1 reduces
both endogenous SP1 and CDK2 protein levels. Hence, IRF1 represses CDK2 gene
expression by interfering with SP1-dependent transcriptional activation. Our
findings establish a causal series of events that functionally connect the
anti-proliferative effects of interferons with the IRF1-dependent suppression of
the CDK2 gene, which encodes a key regulator of the G1/S phase transition.

PMID: 12732645 [PubMed - indexed for MEDLINE]


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