Upregulators
Table 2: Kyn induced genes based on the only microarray analysis (based on Opitz et. al 2011 data)
Upregulators
Phenotype
Location
MYC
Oncogene myc
INDIRECTLY
avian myelocytomatosis viral oncogene homolog
MANIPULATED
protooncogene homologous to myelocytomatosis virus
TARGET
NfKB complex
Inappropriate activation of NF-kappa-B has been linked
10q24.32
to inflammatory events associated with autoimmune
POSSIBLE
arthritis, asthma, septic shock, lung fibrosis,
INDIRECTLY
glomerulonephritis, atherosclerosis, and AIDS.
MANIPULATED
In contrast, complete and persistent inhibition of NFTARGET
kappa-B has been linked directly to apoptosis,
inappropriate immune cell development, and delayed cell
growth.
4q24
Downregulators
ALDH1A3
An unique ALDH isozyme in human saliva
15q26.3
(ALDEHYDE
DEHYDROGENASE 1 FAMILY,
MEMBER A3)
15q25.1
ARNT2,
Member of a novel transcription factor family consisting of a
ARYL HYDROCARBON
conserved basic helix-loop-helix (bhlh) structural motif
RECEPTOR NUCLEAR
contiguous with a PAS domain. Members of this family
TRANSLOCATOR 2
include PER, the aryl hydrocarbon receptor,SIM1,and HIF1A.
4q35.2
C2CD2
Myogenesis in C2C12 mouse myoblasts by DUX4 and
inhibited zebrafish development past gastrulation or caused
severe developmental abnormalities in the surviving
embryos.
11q13.1
CDC42EP2,
A small RHO gtpase, regulates the formation of F-actinCDC42 EFFECTOR PROTEIN 2 containing structures through its interaction with several
downstream effector proteins.
16q22.1
CDH1,
CADHERIN 1;
Uvomorulin, a specific calcium ion-dependent cell adhesion
molecule, expresses its adhesive function during the
preimplantation stage of development and in epithelial cells,
Endometrial carcinoma, somatic, Ovarian carcinoma,
somatic, Gastric cancer, familial diffuse, with or without cleft
lip and/or palate, Breast cancer, lobular, Prostate cancer,
susceptibility to.
CENPA
CENTROMERIC PROTEIN A;
CREB3L2
cAMP RESPONSE ELEMENTBINDING PROTEIN 3-LIKE 2;
CYP1B1,
CYTOCHROME P450,
SUBFAMILY I, POLYPEPTIDE 1
EGR;
EGR1;
Centromeric proteins, see CENPB
2p23.3
Member of the old astrocyte specifically induced substance
(OASIS) DNA binding and basic leucine zipper dimerization
(bzip) family of transcription factors, which includes CREB3
and CREB4.
7q33
Glaucoma 3A, primary open angle, congenital, juvenile,
Or adult onset, Peters anomaly
Discovered first as a putative G0/G1 switch regulatory
gene in human blood lymphocyte cultures and named
G0S30 (Forsdyke, 1985). Sequence analysis of the
murine gene predicted a protein with 3 DNA-binding zinc
fingers
Displays FOS-like induction kinetics in fibroblasts, epithelial
2p22.2
POSSIBLE
TARGET
5q31.2
EARLY GROWTH RESPONSE
1
EREG;
EPIREGULIN
GPR115;
G PROTEIN-COUPLED
RECEPTOR 115
HK2; HEXOKINASE 2
HTT; HUNTINGTON DISEASE
IGFBP4; INSULIN-LIKE
GROWTH FACTOR-BINDING
PROTEIN 4
IL1A; INTERLEUKIN 1-ALPHA
IL1B; INTERLEUKIN 1-BETA
IL6
INTERFERON, BETA-2; IFNB2
B-CELL DIFFERENTIATION
FACTOR, B-CELL
STIMULATORY FACTOR 2;
BSF2, HEPATOCYTE
STIMULATORY FACTOR;
HSF,HYBRIDOMA GROWTH
FACTOR; HGF
IL8
SMALL INDUCIBLE CYTOKINE
SUBFAMILY B, MEMBER 8;
SCYB8, MONOCYTE-DERIVED
NEUTROPHIL CHEMOTACTIC
FACTOR,
NEUTROPHIL-ACTIVATING
PEPTIDE 1; NAP1
GRANULOCYTE
CHEMOTACTIC PROTEIN 1;
GCP1
CHEMOKINE, CXC MOTIF,
LIGAND 8; CXCL8
cells, and lymphocyte. EGR1 is also known as KROX24. Or
nerve growth factor-induced clone A (NGFIA).
Functions as a tumor growth-inhibitory factor inducing
morphologic changes and exhibits low affinity for the EGF
receptor. Found on hela,on human epidermoid carcinoma
A431 cells.
Expression in pregnant uterus, breast, and genitourinary
tract.
Hexokinase (EC 2.7.1.1) catalyzes the first step in glucose
metabolism, using ATP for the phosphorylation of glucose to
glucose-6-phosphate. Four different types of hexokinase,
designated HK1, HK2, HK3, and HK4 (encoded by different
genes, are present in mammalian tissues.
Huntington disease (HD) is caused by an expanded
trinucleotide repeat (CAG)n, encoding glutamine, in the gene
encoding Huntington. An autosomal dominant progressive
neurodegenerative disorder with a distinct phenotype
characterized by chorea, dystonia, incoordination, cognitive
decline, and behavioral difficulties.
Insulin-like growth factor binding proteins (igfbps), such
as IGFBP4, are involved in the systemic and local regulation
of IGF activity. Igfbps contain 3 structurally distinct domains
each comprising approximately one-third of the molecule.).
IL1A is 1 of 2 structurally distinct forms of IL1, the other being
IL1B (147720). The IL1A and IL1B proteins are synthesized
by a variety of cell types, including activated macrophages,
keratinocytes, stimulated B lymphocytes, and fibroblasts, and
are potent mediators of inflammation and immunity
{Gastric cancer risk after H. Pylori infection}
Crohn disease-associated growth, failure}, {Diabetes,
susceptibility to}, {Kaposi sarcoma, susceptibility to},
{Intracranial hemorrhage in brain, Cerebrovascular
malformations, susceptibility to}, {Rheumatoid arthritis,
systemic juvenile}.
A member of the CXC chemokine family.
These small basic heparin-binding proteins are
proinflammatory and primarily mediate the activation
and migration of neutrophils into tissue from peripheral
blood.
(Sukhatme et al.,
1988).
Toyoda et al.
(1995), Toyoda et
al. (1997)
6p12.3
fredriksson et al.
(2002)
POSSIBLE target
2p12
4p16.3
17q21.2
(Kiefer et al., 1992
2q13
(Lord et al., 1991).
2q13
7p15.3
POSSIBLE
COSTIMULATION
TARGET
4q13.3
(Hull et al., 2001).
POSSIBLE
COSTIMULATION
TARGET
ITGAE;
INTEGRIN, ALPHA-E
CD103 ANTIGEN
HUMAN MUCOSAL
LYMPHOCYTE ANTIGEN 1,
ALPHA SUBUNIT
JUN
kiaa1644;
TRIL; TLR4 INTERACTOR
WITH LEUCINE-RICH
REPEATS
LDO C1L
LEUCINE ZIPPER,
DOWNREGULATED IN
CANCER 1; LDOC1
MID1; MIDLINE 1
mir-124; MICRO RNA 124-1
Integrins are a family of cell surface adhesion molecules that
play a major role in diverse cellular and developmental
processes including morphogenesis, hemostasis, leukocyte
activation, cellular adhesion, and homing.
Cerf-Bensussan et
al. (1987),
Parker et al.
(1992)
Immune responses at mucosal sites are mediated by
lymphocytes associated with mammary glands and the
gastrointestinal, genitourinary, and respiratory tracts.
TRIL is a component of the TLR4 complex and is induced in
a number of cell types by lipopolysaccharide (LPS)
7p14.3
(Carpenter et al.,
2009).
Contains a leucine zipper-like motif in its N-terminal
region and a proline-rich region that shares marked
similarity to an SH3-binding domain.
Xq27.1
Nagasaki et al.
(1999)
Northern blot analysis detected ubiquitous expression
of LDOC1 in normal tissues, with high expression in
brain and thyroid and low expression in placenta, liver,
and leukocytes. LDOC1 was expressed in 6 of 7 human
breast cancer cell lines examined, but, with only 1
exception, was not expressed in any pancreatic or
gastric cancer cell lines examined. Fluorescence
microscopy analysis demonstrated that
the LDOC1 protein is located predominantly in the
nucleus.
Midline 1 ring finger gene
midin
finger on x and y, mouse, homolog of; fxy
Opitz gbbb syndrome, type i
Lagos-Quintana et al. (2002) cloned mouse mir124a.
COSTIMULATION
TARGET
xp22.2
Chromosome 8
Northern blot analysis showed that mir124a was highly
expressed in mouse brain, but not in any other mouse tissues
examined.
Suh et al. (2004) cloned human mirna124a from embryonic
stem cells. The mature mirna124a sequence is
UUAAGGCACGCGGUGAAUGCCA.
mir-290
Sempere et al. (2004) found that mirna124 was preferentially
expressed in brain.
Both of the major editing sites in pri-mir-376 rnas (+4 and
+44) are located within the functionally critical 5-primeproximal 'seed' sequences, critical for the hybridization of
mirnas to targets, of mir-376, suggesting that edited
mature mir-376 rnas may target genes different from those
targeted by the unedited mir-376 rnas. Their results
suggested that a single A-I base change is sufficient to
redirect silencing mirnas to a new set of targets.
Editing of mir-376 appears to be one of the mechanisms that
ensure tight regulation of uric acid levels in select tissues
such as the brain cortex. MICRO RNA 376-B; MIRN376B
Kawahara et al.
(2007)
POSSIBLE
COSTIMULATION
TARGET
mir548
RB1;
RB1 GENE
RELA;
V-REL AVIAN
RETICULOENDOTHELIOSIS
VIRAL ONCOGENE
HOMOLOG A
SERPINB2;
SERPIN PEPTIDASE
INHIBITOR,
Clade B (Ovalbumin), Member 2
Plasminogen Activator Inhibitor,
Type 2; Pai2
Planh2
Monocyte Arginine-Serpin
Monocyte-Derived Plasminogen
Activator Inhibitor
Urokinase Inhibitor
SH3RF1; SH3 DOMAINCONTAINING RING FINGER
PROTEIN 2
STC2;
STANNIOCALCIN-RELATED
PROTEIN
TAF9; TAF9 RNA
POLYMERASE II, TATA BOXBINDING PROTEINASSOCIATED FACTOR, 32-KD
TGFB1; TRANSFORMING
GROWTH FACTOR, BETA-1
Bladder cancer, somatic, Osteosarcoma, somatic,
Retinoblastoma, Retinoblastoma, trilateral, Small cell cancer
of the lung, somatic.
13q14.2
Dryja et al. (1984)
NUCLEAR FACTOR KAPPA-B, SUBUNIT 3; NFKB3
TRANSCRIPTION FACTOR NFKB3
NFKB, p65 SUBUNIT
NUCLEAR FACTOR OF KAPPA LIGHT CHAIN GENE
ENHANCER IN B CELLS 3
Activated NFKB complex translocates into the nucleus
and binds DNA at kappa-B-binding motifs such as 5prime GGGRNNYYCC 3-prime or 5-prime HGGARNYYCC
3-prime (where H is A, C, or T; R is an A or G purine; and
Y is a C or T pyrimidine).
11q13.1
POSSIBLE
CO-TIMULATION
TARGET
18q21.33
The specific inhibitors of plasminogen activators have been
classified into 4 immunologically distinct groups: PAI1 type
PA inhibitor from endothelial cells; PAI2 type PA inhibitor
from placenta, monocytes, and macrophages; urinary
inhibitor; and protease-nexin-I.
Plasminogen activator inhibitor-2 is also known as monocyte
arg-serpin because it belongs to the superfamily of serine
proteases in which the target specificity of each is determined
by the amino acid residue located at its reactive center; i.e.,
met or val for elastase, leu for kinase, and arg for thrombin.
Chen et al. (2010) cloned SH3RF2, which they called
HEPP1. The deduced 186-amino acid protein contains a
PP1-binding motif (KTVRFQ). Northern blot analysis detected
1.24- and 0.68-kb HEPP1 transcripts in heart and testis only.
Northern blot analysis revealed that STC2 is expressed as
multiple transcripts in several human tissues, with the
strongest expression in skeletal muscle and heart.
The tafs are required for activated rather than basal
transcription and serve to mediate signals between various
activators and the basal transcriptional machinery.
Camurati-Engelmann disease
5q32
No entry??
5q13.2
19q13.2
{Cystic fibrosis lung disease, modifier of}
TGFB is a multifunctional peptide that controls proliferation, differentiation, and other
synergistically with TGFA (190170) in inducing transformation. It also acts as a negat
activation and signaling may result in apoptosis. Many cells synthesize TGFB and alm
peptide. TGFB1, TGFB2 (190220), and TGFB3 (190230) all function through the sam
TIPARP; TCDD-INDUCIBLE
POLY(ADP-RIBOSE)
POLYMERASE
Amplified and upregulated in head and neck squamous cell
carcinoma (HNSCC). The N-terminal part of the TPH domain
contains a CCCH-type zinc finger.
3q25.31
Katoh and Katoh
(2003) Redon et
al. (2001)
TOP2A
17q21.2
DNA topoisomerase II, resistance to inhibition of, by
amsacrine. DNA topoisomerases (EC 5.99.1.3) are enzymes
that control and alter the topologic states of DNA in both
prokaryotes and eukaryotes.
There are about 100,000 molecules of topoisomerase II per
hela cell nucleus, constituting about 0.1% of the nuclear
extract. In a human leukemia cell line, HL-60/AMSA, Hinds et
al. (1991) found that resistance to inhibition of topoisomerase
II by amsacrine and other intercalating agents was due
To a single base change, AGA (arginine) to AAA (lysine).
TP53; P53
TRANSFORMATION-RELATED
PROTEIN 53; TRP53
Osteosarcoma, Choroid plexus
papilloma, Breast cancer,
Adrenal cortical carcinoma,
Colorectal cancer, Hepatocellular
The transcription factor p53 responds to diverse cellular
stresses to regulate target genes that induce cell cycle arrest,
apoptosis, senescence, DNA repair, or changes in metabolism.
In addition, p53 appears to induce apoptosis through
nontranscriptional cytoplasmic processes.
Activity of p53 is ubiquitously lost in human cancer either by
mutation of the p53 gene itself or by loss of cell signaling
upstream or downstream
17p13.1
The p53 gene (TP53; 191170) is the most frequently mutated
tumor suppressor in human cancers. The ability of p53 to
inhibit cell growth is due, at least in part, to its ability to bind
to specific DNA sequences and activate transcription of
target genes, such as that encoding cell cycle inhibitor
p21(Waf1/Cip1)
Brown et al. (1998) reported that the human ZIC2 gene, a
homolog of the Drosophila 'odd-paired' (opa) gene, maps to
the region of chromosome 13 associated with
holoprosencephaly (HPE5; 609637). Have zinc finger
domain.
Holoprosencephaly-5
Holoprosencephaly is the most common structural anomaly
of the human brain and is one of the anomalies seen in
patients with deletions and duplications of chromosome 13
1p36.32
POSSIBLE
TARGET FOR COSTIMULATION
carcinoma, Li-Fraumeni syndrome,
Nasop haryngeal carcinoma,
Pancreatic cancer, {Glioma
susceptibility 1}, {Basal cell
carcinoma 7}
TP73; p53-RELATED PROTEIN
p73; p73
TRP73, MOUSE, HOMOLOG
OF
ZIC2; ZIC FAMILY MEMBER 2
13q32.3