Most individuals with cystic fibrosis (CF) carry one or two mutations that result in a maturation defect of the full-length CFTR protein. The deltaF508 mutation results in a mutant protein that is degraded by the proteasome instead of progressing to the apical membrane where it functions as a cyclic AMP-regulated chloride channel. 4 phenylbutyrate modulates heat shock protein expression and promotes trafficking of deltaF508 thus permitting maturation and membrane insertion. The goal of this study was to gain insight into the genetic mechanism of PBA action through a large-scale analysis of gene expression. The Affymetrix genome spanning U133 microarray set was used to compare mRNA expression in untreated IB3-1 cell line cultures with cultures treated with 1mM 4-phenylbuyterate for 12 and 24 hr. IB3-1 deltaF508/W1282X) bronchial epithelial cells were cultured in T75 flasks with gentamicin-free LHC-8 medium. Cells were fed with 10 ml of media every 2 to 3 days. After reaching 80% confluence cells were treated with 1 mM PBA. A T75 flask of confluent IB3-1 cells was rinsed twice with ice cold Hank’s buffer then scraped into 3ml of ice cold TRIzol (Gibco BRL) then rinsed with 3 ml ice cold TRIzol and the mRNA was isolated according to the TRIzol protocol. A total of 5 control cultures, 3 cultures with 12 hr BPA application and 3 cultures with 24 hr PBA application were processed Keywords: time-course
XM_043151; Both Celera and NCBI find same domain, otherwise uncharacterized; ortholog of mouse adp-ribosylation-like factor 6 interacting protein 2 (2-blast 85% identity); Guanylate-binding protein, N-terminal domain. Transcription of the anti-viral guanylate-binding protein (GBP) is induced by interferon-gamma during macrophage induction. This family contains GBP1 and GPB2, both GTPases capable of binding GTP, GDP and GMP
244030_at
1.4802725
0.9826246
0.8801376
STYX
NM_145251
NM_145251; serine/threonine/tyrosine interacting protein;STYX domain adds to the repertoire of modular domains that can mediate intracellular signaling in response to protein phosphorylation
RNA
231843_at
1.4336354
1.0347776
0.84700286
KIAA1595
XM_045520
pfam- DEAD-like helicase superfamily. The DEAD box helicases are involved in various aspects of RNA metabolism, including nuclear transcription, pre mRNA splicing, ribosome biogenesis, nucleocytoplasmic transport, translation, RNA decay and organellar gene expression.
227110_at
1.4029067
1.0758003
0.6353888
HNRPC
NM_031314
heterogeneous nuclear ribonucleoprotein C (C1/C2); Ariadne-2 protein homolog (ARI-2) (Triad1 protein).These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. 2 isoforms NM_004500, NM_031314
224714_at
1.5301582
1.0806509
0.6697256
MKI67IP
NM_032390
Interacts with nucleolar phosphoprotein through Forkhead associated domain on pKi-67. Pfam- RNA binding protein. PMID: 11342549
224523_s_at
1.4159906
1.0787356
0.6358406
MGC4308
NM_032359
pfam - DEAD/DEAH box helicase- involved in unwinding nucleic acids and various aspects of RNA metabolism
222398_s_at
1.4112586
1.1386119
0.6309118
U5-116KD
NM_004247
U5 snRNP-specific protein. pfam03144 Elongation factor Tu domain 2. Elongation factor Tu consists of three structural domains. This, the second domain, is involved in binding to charged tRNA. This domain is also found in other proteins such as elongation factor G and translation initiation factor IF-2
204658_at
1.4334122
1.1078998
0.65938324
HSU53209
NM_013293
pre-mRNA processing factor; Homo sapiens transformer-2 alpha (htra-2 alpha). RNA binding protein domains
222430_s_at
1.4146345
1.0326276
0.6482412
HGRG8
NM_016258
Homo sapiens, high-glucose-regulated protein 8. Pfam- putative splicing factor, tyrosine-phosphoylated nuclear protein
218156_s_at
1.6291847
0.88601065
0.43491048
FLJ10534
NM_018128
CDD:COG5192, BMS1, GTP-binding protein required for 40S ribosome biogenesis [Translation, ribosomal structure and biogenesis]. NCBI annotates protein as a serine racemase
225348_at
1.3855543
1.0138597
0.6366804
FUSIP1
AK001479
NM_006625; FUS interacting protein (serine-arginine rich) 1 isoform 1 NM_021993; NM_054016; FUS interacting protein (serine-arginine rich) 1 isoform 2; NM_021993 replaced by NM_054016; Member of the serine-arginine (SR) family of proteins, which is involved in constitutive and regulated RNA splicing. Members of this family are characterized by N-terminal RNP1 and RNP2 motifs, which are required for binding to RNA, and multiple C-terminal SR/RS repeats, which are important in mediating association with other cellular proteins.
231718_at
1.4222896
0.8014412
0.66037893
SLU7
NM_006425
step II splicing factor SLU7. functions in restructuring the spliceosome between the catalytic steps of splicing
222443_s_at
1.5378356
1.2278483
0.7533718
RBM8A
NM_005105
RNA binding motif protein 8A
223035_s_at
1.3986365
1.2125903
0.8051443
FRSB
NM_005687
phenylalanyl-tRNA synthetase beta-subunit.
223416_at
1.3777913
1.2366493
0.8330658
CGI-110
NM_016047
CGI-110 protein, RNA binding domain
244811_at
1.6487906
1.3381889
0.8538915
EEF1E1
AI561173
NM_004280; eukaryotic translation elongation factor 1 epsilon 1; COG - Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones] transferase function not demonstrated in EEF1E1 but domain is also found in HSP26 family of stress response proteins
PMP70; PXMP1; ABC43; Peroxisomal membrane protein-1 (70kD); ATP-binding cassette, sub-family D (ALD), member 3 (ABCD3). Pfam-ABC transporter. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ALD subfamily, which is involved in peroxisomal import of fatty acids and/or fatty acyl-CoAs in the organelle. All known peroxisomal ABC transporters are half transporters which require a partner half transporter molecule to form a functional homodimeric or heterodimeric transporter. This peroxisomal membrane protein likely plays an important role in peroxisome biogenesis.
Signaling
204115_at
0.87040347
1.8637396
0.7688593
GNG11
NM_004126
Homo sapiens guanine nucleotide binding protein 11. Pfam - domain found in gamma subunit of heteromeric G protein complex and in regulators of g protein signaling.
225171_at
1.0462258
1.5612801
0.6427184
MacGAP
NM_033515
pfam-GTPase-activator protein for Rho-like GTPases
Cell fate
201324_at
0.881943
1.9566708
0.4844489
EMP1
NM_001423
TMP; CL-20; Epithelial membrane protein 1. CDD: PMP22_Claudin common to small integral membrane glycoproteins which contain 4 transmembrane segments and appear involved in cell proliferation
201421_s_at
1.2474958
1.6677381
0.8320047
MEP50
NM_024102
MGC2722; Homo sapiens MEP50 protein (MEP50). Pfam - WD40 found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly
207030_s_at
0.734624
1.7776583
1.1605697
CSRP2
NM_001321
CRP2; LMO5; SmLIM; LIM domain only 5, smooth muscle; Homo sapiens cysteine and glycine-rich protein 2. Pfam - LIM domain, binds 2 zinc ions but appears to act as interface for protein-protein interactions rather than DNA binding. Possibly involved in cell growth and differentiation. PMID: 11672422 potential new factor in the JAK/STAT-signalling pathway
214051_at
0.96047467
1.7146008
0.9357601
TMSNB
NM_021992
thymosin beta, which is highly conserved acidic polypeptide, originally isolated from calf thymus. Changes in the expression of beta-thymosins appear to be related to the differentiation of cells. Among the effects are induction of metallo-proteinases, chemotaxis, angiogenesis and inhibition of inflammation as well as the inhibition of bone marrow stem cell proliferation
Enzymes
230333_at
0.9743934
2.081771
0.86801493
SAT
Z14136
spermidine/spermine N1-acetyltransferase. NM_002970 is supposed to be same gene but no target sequence match.
221750_at
0.9834293
1.8827162
0.8663183
HMGCS1
NM_002130
3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1; expression promoted by butyrate
Transcription
201417_at
0.84249127
1.9114044
1.2865078
SOX4
NM_003107
Homo sapiens SRY (sex determining region Y)-box 4. CDD: HMG - high mobility group - binds single-stranded DNA and unnwinds double stranded DNA. Low molecular weight non-histone components in chromatin. Occurs in SOX family of transcription factors.
202133_at
0.80852044
1.5695218
0.7611693
TAZ
NM_015472
Transcriptional co-activator with PDZ-binding motif. Pfam WW domain binds to proline-rich peptide motifs
208937_s_at
0.6953585
1.7443362
0.91894764
ID1
NM_002165
inhibitor of DNA binding 1, dominant negative helix-loop-helix protein. Pfam - HLH binding domain
Protein processing
202194_at
1.0226113
1.6430582
0.7526694
CGI-100
NM_016040
emp24/gp25L/p24 family. Members of this Pfam are implicated in bringing cargo forward from the ER and binding to coat proteins by their cytoplasmic domains
Homo sapiens alanyl-tRNA synthetase. CDD: t-rna synthethase; DHHA1 associated with DHH domain - probably RNA binding function
202725_at
1.307531
0.8682454
2.4323015
POLR2A
NM_000937
RPB1; RPO2; POLR2; POLRA; RPBh1; RPOL2; RpIILS; hsRPB1; hRPB220; polymerase (RNA) II (DNA directed) polypeptide A (220kD); DNA-directed RNA polymerase II largest subunit, RNA polymerase II 220 kd subunit; Homo sapiens polymerase (RNA) II (DNA directed) polypeptide A, 220kDa (POLR2A), mRNA.
212971_at
1.1256014
0.78184724
1.7553929
CARS
NM_139273
cysteinyl-tRNA synthetase, transcript variant 1. Pfam - tRNA synthetase class I � and (I,L,M and V)
Enzymes
204151_x_at
0.8578472
1.117119
1.690151
AKR1C1
NM_001353
DD1; DDH; DDH1; H-37; HBAB; MBAB; HAKRC; 2-ALPHA-HSD; 20-ALPHA-HSD; dihydrodiol dehydrogenase 1 (trans-1,2-dihydrobenzene-1,2-diol dehydrogenase, high affinity bile acid binding); type II 3-alpha-HSD; Pfam - family includes some K+ ion channel beta chain regulatory domains predicted to have oxidreductase activity; metabolizes neurosteroids derived from progesterone.
Control of gene expression
225263_at
0.95783925
0.9463855
1.5714557
HS6ST
BC001196
NM_004807; heparan sulfate 6-O-sulfotransferase; type II integral membrane protein; Heparan sulfate, an abundant component of the cell surface and the extracellular matrix, is involved in a variety of biological processes such as growth factor signaling, cell adhesion, and enzymatic catalysis; possible an evolutionally conserved role for 6-O-sulfated heparan sulfate in FGF signaling.
39966_at
0.65044695
1.2297151
1.8618413
CSPG5
NM_006574
chondroitin sulfate proteoglycan 5 (neuroglycan C). Supposed to be neural tissue specific
Signalling
215735_s_at
1.6807154
0.6690282
1.6052006
TSC2
AC005600
NM_000548; tuberous sclerosis 2 isoform 1 NM_021055; tuberous sclerosis 2 isoform 2 NM_021056; functions as a Rab5 GTPase activating protein (GAP) in vivo to negatively regulate Rab5-GTP activity in endocytosis
210999_s_at
1.1890529
0.7820127
1.6137617
GRB10
NM_005311
growth factor receptor-bound protein 10. Pfam PH - eukaryotic signaling protein, bind to inositol phosphates and other proteins. Pfam SH2 related to smart00252 - bind phosphotyrosine-containing polypeptides
225768_at
1.0700499
0.95432526
2.0508904
NR1D2
AI761621
NM_005126; nuclear (hormone) receptor subfamily 1, group D, member 2
219429_at
0.8812924
1.2887502
1.7910409
FAAH
NM_024306
fatty acid hydroxylase; appears to play a major role in regulating the amplitude and duration of FAA class of signaling lipids in vivo (neurobehavioral response)
Transporter
224609_at
0.7983619
0.7132844
1.6059637
CTL2
NM_020428
choline transporter-like protein. At 8 or 9 potential transmembrane regions
204981_at
1.146335
0.9852024
1.6053233
SLC22A1L
NM_002555
HET; ITM; BWR1A; IMPT1; TSSC5; ORCTL2; BWSCR1A; p45-BWR1A; p45 Beckwith-Wiedemann region 1A; Beckwith-Wiedemann syndrome chromosome region 1, candidate A; efflux transporter-like protein; organic cation transporter-like 2; tumor-suppressing STF cDNA 5; imprinted multi-membrane spanning polyspecific transporter-related protein; Homo sapiens solute carrier family 22 (organic cation transporter), member 1-like (SLC22A1L), mRNA.
Glutathione
201348_at
0.7842046
1.0969342
1.5792764
GPX3
NM_002084
glutathione peroxidase 3 (plasma) (GPX3), mRNA.
202967_at
1.0946716
1.2513615
1.8354115
GSTA4
NM_001512
GTA4; GSTA4-4; Belongs to the alpha gene class GST family; glutathione S-alkyltransferase A4; glutathione S-aryltransferase A4; S-(hydroxyalkyl)glutathione lyase A4; glutathione S-aralkyltransferase A4; glutathione transferase A4-4; GST class-alpha; glutathione S-transferase, alpha 4; Homo sapiens glutathione S-transferase A4 (GSTA4), mRNA.
Total number of rows: 39
Table truncated, full table size 7 Kbytes.
Genes involved in ER unfolded protein response header descriptions
All data per gene
Data table
All data per gene
Time (hours)
0
12
24
Affy ID
Normalized
Normalized
Normalized
Common
Genbank
Description
239996_x_at
0.96938837
1.074118
1.5431569
ATP2A2
AI671237
wb14h10.x1 NCI_CGAP_GC6 Homo sapiens cDNA clone IMAGE:2305699 3' similar to contains TAR1.t2 MER22 MER22 repetitive element ;, mRNA sequence.
201216_at
0.88684005
0.9190469
1.033773
C12orf8
NM_006817
ERP28; ERP29; PDI-DB; endoplasmic reticulum lumenal protein ERp28; Homo sapiens chromosome 12 open reading frame 8 (C12orf8), mRNA.
205625_s_at
1.0642792
1.1601409
0.48469606
CALB1
AW014927
UI-H-BI0-aaf-f-06-0-UI.s1 NCI_CGAP_Sub1 Homo sapiens cDNA clone IMAGE:2709251 3', mRNA sequence.
tb60a01.x1 NCI_CGAP_Br15 Homo sapiens cDNA clone IMAGE:2058696 3' similar to gb:M84739 CALRETICULIN PRECURSOR (HUMAN);, mRNA sequence.
200935_at
0.9486014
1.005216
1.0650926
CALR
NM_004343
SSA; RO; This protein was initially named autoantigen Ro but this property was later disputed; Sicca syndrome antigen A (autoantigen Ro; calreticulin); Homo sapiens calreticulin (CALR), mRNA.
212952_at
1.0267859
1.2833138
1.057845
CALR
BE251303
601107814F1 NIH_MGC_16 Homo sapiens cDNA clone IMAGE:3344018 5', mRNA sequence.
228091_at
0.9631158
0.85651624
1.1750785
CALR
AI800609
wg12e06.x1 Soares_NSF_F8_9W_OT_PA_P_S1 Homo sapiens cDNA clone IMAGE:2364898 3', mRNA sequence.
214316_x_at
0.6254221
1.1562779
0.9962828
CALR
AI348935
tb60a01.x1 NCI_CGAP_Br15 Homo sapiens cDNA clone IMAGE:2058696 3' similar to gb:M84739 CALRETICULIN PRECURSOR (HUMAN);, mRNA sequence.
212953_x_at
1.0379649
1.050335
1.1154665
CALR
BE251303
601107814F1 NIH_MGC_16 Homo sapiens cDNA clone IMAGE:3344018 5', mRNA sequence.
238034_at
1.0392767
0.8721512
0.9684489
CANX
AI890021
wm80f04.x1 NCI_CGAP_Ut2 Homo sapiens cDNA clone IMAGE:2442271 3', mRNA sequence.
208852_s_at
1.0916346
0.90162367
0.8187067
CANX
AI761759
wg67h12.x1 Soares_NSF_F8_9W_OT_PA_P_S1 Homo sapiens cDNA clone IMAGE:2370215 3' similar to gb:L10284 CALNEXIN PRECURSOR (HUMAN);, mRNA sequence.
200068_s_at
1.3080641
1.222996
0.9946158
CANX
M94859
Human calnexin mRNA, complete cds.
208853_s_at
0.99536645
1.0841155
0.81595665
CANX
L18887
Human calnexin mRNA, complete cds.
209476_at
1.2032287
1.2263522
0.8189533
DKFZp564E1962
AL080080
similarity to protein disulphide isomerases; Homo sapiens mRNA; cDNA DKFZp564E1962 (from clone DKFZp564E1962); partial cds.
208370_s_at
1.0720677
1.0199797
0.91292125
DSCR1
NM_004414
MCIP1; ADAPT78; Down syndrome candidate region 1; near DSCR proline-rich protein; human Down syndrome candidate region protein, proline-rich protein; Homo sapiens Down syndrome critical region gene 1 (DSCR1), mRNA.
Less...
More...