1: Immunogenetics. 2005 Jan;56(10):710-21. Epub 2004 Dec 1. 

Characterization of two genes encoding leucine-rich repeat-containing proteins
in grass carp Ctenopharyngodon idellus.

Chang MX, Nie P, Xie HX, Sun BJ, Gao Q.

State Key Laboratory of Freshwater Ecology and Biotechnology, Chinese Academy of
Sciences, Wuhan, 430072, Hubei Province, PR China. pinnie@ihb.ac.cn

The cDNAs and genes of two different types of leucine-rich repeat-containing
proteins from grass carp (Ctenopharyngodon idellus) were cloned. Homology search
revealed that the two genes, designated as GC-GARP and GC-LRG, have 37% and 32%
deduced amino-acid sequence similarities with human glycoprotein A repetitions
predominant precursor (GARP) and leucine-rich alpha2-glycoprotein (LRG),
respectively. The cDNAs of GC-GARP and GC-LRG encoded 664 and 339 amino acid
residues, respectively. GC-GARP and GC-LRG contain many distinct structural
and/or functional motifs of the leucine-rich repeat (LRR) subfamily, such as
multiple conserved 11-residue segments with the consensus sequence LxxLxLxxN/CxL
(x can be any amino acid). The genes GC-GARP and GC-LRG consist of two exons,
with 4,782 bp and 2,119 bp in total length, respectively. The first exon of each
gene contains a small 5'-untranslated region and partial open reading frame. The
putative promoter region of GC-GARP was found to contain transcription factor
binding sites for GATA-1, IRF4, Oct-1, IRF-7, IRF-1, AP1, GATA-box and NFAT, and
the promoter region of GC-LRG for MYC-MAX, MEIS1, ISRE, IK3, HOXA9 and C/EBP
alpha. Phylogenetic analysis showed that GC-GARP and mammalian GARPs were
clustered into one branch, while GC-LRG and mammalian LRGs were in another
branch. The GC-GARP gene was only detected in head kidney, and GC-LRG in the
liver, spleen and heart in the copepod (Sinergasilus major)-infected grass carp,
indicating the induction of gene expression by the parasite infection. The
results obtained in the present study provide insight into the structure of fish
LRR genes, and further study should be carried out to understand the importance
of LRR proteins in host-pathogen interactions.

PMID: 15578176 [PubMed - indexed for MEDLINE]


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2: Mol Cancer Res. 2003 Jun;1(8):619-30. 

Identification and characterization of retinoic acid receptor beta2 target genes
in F9 teratocarcinoma cells.

Zhuang Y, Faria TN, Chambon P, Gudas LJ.

Pharmacology Department, Weill Medical College of Cornell University, New York,
NY, USA.

Retinoids, a group of natural and synthetic analogues of vitamin A (retinol),
modulate the differentiation of many cell types. Retinoids are also used for the
prevention and treatment of cancer. The actions of retinoids are generally
mediated by the retinoic acid receptors (RARs alpha, beta, and gamma) and the
retinoid X receptors (RXRs alpha, beta, and gamma). One of the RARs, RARbeta, is
expressed at reduced levels in many human carcinomas, and F9 RARbeta(2)(-/-)
cells do not growth arrest in response to RA. To determine if RARbeta(2)
regulates the expression of a unique set of genes, through the use of
subtractive hybridization and DNA array analysis, we have identified and
characterized genes that are differentially expressed in F9 RARbeta(2)(-/-)
teratocarcinoma cells. These genes, which encode transcription factors, cell
surface signal transduction molecules, and metabolic enzymes, include c-myc,
FOG1, GATA6, glutamate dehydrogenase, glutathione S-transferase homologue (p28),
Foxq1, Hic5, Meis1a, Dab2, midkine, and the PDGF-alpha receptor. These genes are
regulated specifically by RARbeta(2) in F9 wild-type (Wt) cells as indicated by
their expression profiles in F9 RARbeta(2)(-/-) cells as compared to F9 Wt,
RARalpha(-/-), or RARgamma(-/-) cells, and their responsiveness to specific
retinoid receptor agonists. The basal expression levels of some of these genes,
such as c-myc, are higher in the F9 RARbeta(2)(-/-) cells than in F9 Wt in the
absence of exogenous retinoids, suggesting that RARbeta(2) can inhibit gene
expression in the absence of a ligand. The RARbeta(2) target genes are
transcriptionally activated by retinol, as well as RA, in F9 Wt cells. Because
the lack of RARbeta(2) alters both the control of proliferation and
differentiation in F9 cells, the genes that we have characterized may mediate
key effects of RA, via RARbeta(2), on these processes.

PMID: 12805409 [PubMed - indexed for MEDLINE]


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3: Blood. 2003 Jul 1;102(1):262-8. Epub 2003 Mar 13. 

Gene expression signatures in MLL-rearranged T-lineage and B-precursor acute
leukemias: dominance of HOX dysregulation.

Ferrando AA, Armstrong SA, Neuberg DS, Sallan SE, Silverman LB, Korsmeyer SJ,
Look AT.

Department of Pediatric Oncology, Mayer-630, Dana-Farber Cancer Institute, 44
Binney Street, Boston, MA 02115, USA.

Rearrangements of the MLL locus, located on human chromosome 11q23, are frequent
in both infant and therapy-related leukemias. Gene expression analysis of
MLL-rearranged B-precursor acute lymphoblastic leukemias (MLL B-ALLs) has
identified these cases as a unique subtype of leukemia, characterized by the
expression of genes associated with both lymphoid and myeloid hematopoietic
lineages. Here we show that MLL fusions also generate a distinct genetic subtype
of T-lineage ALL (MLL T-ALL), in which leukemic cells are characterized by an
early arrest in thymocyte differentiation, with suggestive evidence of
commitment to the gammadelta lineage. Interestingly, multiple genes linked to
cell proliferation (eg, PCNA, MYC, CDK2, and POLA) were down-regulated in
MLL-fusion samples, relative to those transformed by other T-ALL oncogenes (P
<.000 001, Fisher exact test). Overall, MLL T-ALL cases consistently
demonstrated increased levels of expression of a subset of major HOX
genes--HOXA9, HOXA10, and HOXC6--and the MEIS1 HOX coregulator (P <.008,
one-sided Wilcoxon test), a pattern of gene expression that was reiterated in
MLL B-ALLs. However, expression of myeloid lineage genes, previously reported in
MLL B-ALLs, was not identified in T-lineage cases with this abnormality,
suggesting that myeloid gene dysregulation is dispensable in leukemic
transformation mediated by MLL fusion proteins. Our findings implicate
dysregulation of HOX gene family members as a dominant mechanism of leukemic
transformation induced by chimeric MLL oncogenes.

PMID: 12637319 [PubMed - indexed for MEDLINE]


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