Protein Array Based Interactome Analysis of Amyloid-β Indicates an Inhibition of Protein Translation
Dezso P. Virok*†Dóra Simon‡
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Publication Date:January 19, 2011
Oligomeric
amyloid-β is currently of interest in amyloid-β mediated toxicity and
the pathogenesis of Alzheimer’s disease. Mapping the amyloid-β
interaction partners could help to discover novel pathways in disease
pathogenesis. To discover the amyloid-β interaction partners, we applied
a protein array with more than 8100 unique recombinantly expressed
human proteins. We identified 324 proteins as potential interactors of
oligomeric amyloid-β. The Gene Ontology functional analysis of these
proteins showed that oligomeric amyloid-β bound to multiple proteins
with diverse functions both from extra and intracellular localizations.
This undiscriminating binding phenotype indicates that multiple protein
interactions mediate the toxicity of the oligomeric amyloid-β. The most
highly impacted cellular system was the protein translation machinery.
Oligomeric amyloid-β could bind to altogether 24 proteins involved in
translation initiation and elongation. The binding of amyloid-β to
purified rat hippocampal ribosomes validated the protein array results.
More importantly, in vitro translation assays showed that the
oligomeric amyloid-β had a concentration dependent inhibitory activity
on translation. Our results indicate that the inhibited protein
synthesis is one of the pathways that can be involved in the
amyloid-beta induced neurotoxicity.
KEYWORDS (keywords):
Alzheimer’s
oligomeric
amyloid-β
protein array
protein chip
proteomics
interactome
Alzheimer’s
oligomeric
amyloid-β
protein array
protein chip
proteomics
interactome
normalized signal intensity
Protein Header Gene Symbol Database ID Ultimate ORF ID Swissprot ID Array A Array B
P2293 7110,22 7245,60
PV4690 6835,22 8718,84
WD repeat domain 5 (WDR5), transcript variant 1 WDR5 NM_017588.1 IOH4895 P61964 6279,74 8539,23
signal recognition particle 19kDa (SRP19) SRP19 BC010947.1 IOH14455 P09132 6076,43 3232,90
hypothetical protein MGC42630 (MGC42630) FAM27E3 NM_175923.2 IOH22051 Q08E93 4909,23 4141,35
SUMO1/sentrin/SMT3 specific peptidase 2 (SENP2) SENP2 NM_021627.2 IOH26311 Q9HC62 3572,22 4621,71
DEAD (Asp-Glu-Ala-Asp) box polypeptide 18 (DDX18) DDX18 BC003360.1 IOH2892 Q9NVP1 3569,76 5607,45
RNA binding motif protein 11 (RBM11) RBM11 NM_144770.1 IOH22581 P57052 3386,34 2756,28
chromosome 12 open reading frame 52 (C12orf52) C12orf52 NM_032848.1 IOH13466 Q96K30 3103,24 5477,67
variable charge, Y-linked 1B (VCY) VCY BC056508.1 IOH29456 O14598 2827,13 3931,10
SECIS binding protein 2 (SECISBP2) SECISBP2 BC036109.1 IOH27253 Q96T21 2813,28 9535,04
hexokinase 1 (HK1) HK1 BC008730.2 IOH5942 P19367 2756,41 2624,89
Pumilio domain-containing protein KIAA0020 KIAA0020 NM_014878.2 IOH10030 Q15397 2648,09 3024,14
LTV1 homolog (S. cerevisiae) (LTV1) LTV1 NM_032860.2 IOH22948 Q96GA3 2627,18 1946,10
PP2C-like domain-containing protein C3orf48 C3orf48 NM_144714.1 IOH11221 A8MPX8 2626,93 4930,28
zinc finger protein 22 (KOX 15) (ZNF22) ZNF22 BC010642.1 IOH9701 P17026 2618,53 4538,58
olfactory receptor, family 6, subfamily B, member 3 (OR6B3), mRNA OR6B3 AB065662.1 IOH28287 Q8NGW1 2549,07 999,95
chromosome 3 open reading frame 37 (C3orf37) C3orf37 BC009993.2 IOH27830 Q96FZ2 2491,57 2484,15
guanine nucleotide binding protein-like 2 (nucleolar) (GNL2) GNL2 BC009250.1 IOH27775 Q13823 2316,56 4556,13
tubulin, gamma 1 (TUBG1) TUBG1 NM_001070.1 IOH4241 P23258 2312,38 3332,08
PDZ domain-containing protein 4 PDZD4 BC002606.1 IOH4132 Q76G19 2228,66 2043,16
arginine vasopressin-induced 1 (AVPI1) AVPI1 BC000877.1 IOH3268 Q5T686 2211,16 1588,71
general transcription factor IIE, polypeptide 2, beta 34kDa (GTF2E2) GTF2E2 NM_002095.1 IOH22963 P29084 2205,65 2998,21
occludin/ELL domain containing 1 (OCEL1) OCEL1 NM_024578.1 IOH23128 Q9H607 2186,50 2493,36
fibroblast growth factor 12 (FGF12), transcript variant 1 FGF12 NM_021032.2 IOH35339 P61328 2184,15 1519,12
ets variant gene 3 (ETV3) ETV3 NM_005240.1 IOH13301 P41162 2123,09 4535,51
PIN2-interacting protein 1 (PINX1) PINX1 BC015479.1 IOH11268 Q96BK5 2117,48 1544,14
nucleolar and coiled-body phosphoprotein 1 (NOLC1) NOLC1 BC006769.1 IOH3146 Q14978 2107,19 6902,87
small nuclear ribonucleoprotein 70kDa polypeptide (RNP antigen) (SNRP70) SNRP70 NM_003089.4 IOH40192 P08621 2104,52 6018,96
TATA box binding protein (TBP)-associated factor, RNA polymerase I, B, 63kDa (TAF1B) TAF1B BC018137.1 IOH10369 Q53T94 2100,47 2874,62
ribosomal protein L31 (RPL31), transcript variant 1 RPL31 NM_000993.2 IOH14051 P62899 2099,69 2492,06
ribosomal protein S16 (RPS16) RPS16 NM_001020.2 IOH13828 P62249 2054,42 3402,04
Phytanoyl-CoA dioxygenase domain-containing protein 1 PHYHD1 NM_174933.2 IOH12686 Q5SRE7 2007,02 1534,02
fibroblast growth factor 12 (FGF12), transcript variant 2 FGF12 NM_004113.3 IOH34727 P61328 1998,76 2687,61
activator of basal transcription 1 (ABT1) ABT1 NM_013375.2 IOH1920 Q9ULW3 1961,12 1638,59
eukaryotic translation initiation factor 2C, 1 (EIF2C1) EIF2C1 BC063275.1 IOH40423 Q9UL18 1951,40 2309,47
mitochondrial ribosomal protein S18A (MRPS18A), nuclear gene encoding mitochondrial protein MRPS18A NM_018135.2 IOH12060 Q9NVS2 1921,66 2847,10
DEAD (Asp-Glu-Ala-Asp) box polypeptide 10 (DDX10) DDX10 NM_004398.2 IOH38427 Q13206 1900,80 2427,42
zinc finger protein 684 (ZNF684) ZNF684 NM_152373.2 IOH14361 Q5T5D7 1893,68 3233,24
intestinal cell (MAK-like) kinase (ICK), transcript variant 1 ICK NM_014920.2 IOH38087 Q9UPZ9 1888,31 1321,44
glyceraldehyde-3-phosphate dehydrogenase (GAPDH) GAPDH NM_002046.2 IOH3380 P04406 1857,17 1394,76
bobby sox homolog (Drosophila) (BBX) BBX NM_020235.2 IOH44025 Q8WY36 1843,23 5121,71
chromosome 18 open reading frame 56 (C18orf56) C18orf56 BC028301.1 IOH11759 Q8TAI1 1837,02 1453,78
zinc finger protein 747 (ZNF747) ZNF747 NM_023931.1 IOH3950 Q9BV97 1832,78 3096,57
fibroblast growth factor 13 (FGF13), transcript variant 1A FGF13 NM_004114.2 IOH13832 Q92913 1818,27 1295,24
MYB binding protein (P160) 1a (MYBBP1A) MYBBP1A BC050546.1 IOH26928 Q9BQG0 1796,01 2583,47
UTP14, U3 small nucleolar ribonucleoprotein, homolog A (yeast) (UTP14A) UTP14A BC001149.1 IOH4457 Q9BVJ6 1768,08 3006,02
calcium/calmodulin-dependent protein kinase kinase 2, beta (CAMKK2) CAMKK2 BC026060.2 IOH12294 Q96RR4 1751,72 2227,90
v-myc myelocytomatosis viral oncogene homolog (avian) (MYC) MYC BC000141.1 IOH2954 P01106 1706,09 740,84
dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 2 (DYRK2), transcript variant 1 DYRK2 NM_003583.2 IOH2412 Q92630 1683,98 1931,17
RNA binding motif protein 34 (RBM34) RBM34 NM_015014.1 IOH23193 P42696 1682,76 1236,80
zinc finger CCCH-type containing 3 (ZC3H3) ZC3H3 BC034435.1 IOH21500 Q8IXZ2 1660,73 3548,28
inhibitor of growth family, member 2 (ING2) ING2 NM_001564.1 IOH22913 Q9H160 1635,98 2687,19
ubiquitin specific peptidase 2 (USP2) USP2 BC002955.1 IOH4931 O75604 1625,07 1150,06
zinc finger protein 622 (ZNF622) ZNF622 NM_033414.1 IOH10240 Q969S3 1581,93 1041,84
TGF-beta receptor type-2 TGFBR2 BC040499.1 IOH27240 P37173 1577,35 1738,98
Fanconi anemia, complementation group M (FANCM) FANCM BC036056.1 IOH27184 Q8IYD8 1577,11 2227,13
THAP domain containing 4 (THAP4) THAP4 NM_015963.4 IOH40797 Q8WY91 1563,75 1797,27
PHD finger protein 8 (PHF8) PHF8 BC053861.1 IOH28930 Q9UPP1 1515,09 2104,93
chromosome 9 open reading frame 43 (C9orf43) C9orf43 NM_152786.1 IOH11171 Q8TAL5 1456,72 1888,16
cytoplasmic polyadenylation element binding protein 1 (CPEB1) CPEB1 BC035348.1 IOH28673 Q9BZB8 1455,67 2662,34
histone cluster 2, H2ac (HIST2H2AC) HIST2H2AC NM_003517.2 IOH29296 Q16777 1448,87 1904,62
Uncharacterized protein C7orf50 C7orf50 NM_032350.3 IOH6347 Q9BRJ6 1447,63 1941,87
ADAM metallopeptidase domain 22 (ADAM22) ADAM22 BC036029.1 IOH27232 Q9P0K1 1439,91 1768,58
excision repair cross-complementing rodent repair deficiency, complementation group 1 (includes overlapping antisense sequence) (ERCC1) ERCC1 BC052813.1 IOH29045 P07992 1436,51 778,43
pescadillo homolog 1, containing BRCT domain (zebrafish) (PES1) PES1 NM_014303.2 IOH21738 O00541 1427,79 1551,73
suppressor of cytokine signaling 5 (SOCS5) SOCS5 BC032862.1 IOH27139 O75159 1407,51 2254,47
dpy-19-like 2 pseudogene 4 (C. elegans) (DPY19L2P4) LOC554208 BC047471.1 IOH26529 Q86X12 1406,77 1943,02
Protein ZNF365 ZNF365 BC070073.1 IOH40070 Q70YC5 1403,99 2140,75
Wolf-Hirschhorn syndrome candidate 1 (WHSC1), transcript variant 5 WHSC1 NM_133332.1 IOH38113 O96028 1401,24 2409,90
protein tyrosine phosphatase, non-receptor type 12 (PTPN12) PTPN12 NM_002835.2 IOH28818 Q05209 1373,53 1801,50
ankyrin repeat and zinc finger domain containing 1 (ANKZF1) ANKZF1 BC000238.1 IOH4394 Q9H8Y5 1370,61 2532,16
ribosomal protein L3-like (RPL3L) RPL3L NM_005061.2 IOH26731 Q92901 1362,03 1458,56
IMP4, U3 small nucleolar ribonucleoprotein, homolog (yeast) (IMP4) IMP4 NM_033416.1 IOH12991 Q96G21 1358,14 1653,58
chromosome 8 open reading frame 33 (C8orf33) C8orf33 NM_023080.1 IOH13369 Q9H7E9 1355,97 1557,62
activation-induced cytidine deaminase (AICDA) AICDA NM_020661.1 IOH6382 Q546Y9 1355,44 1363,86
ligand of numb-protein X 1 (LNX1) LNX1 BC022983.1 IOH10747 Q8TBB1 1346,43 2079,80
death effector domain containing (DEDD), transcript variant 2 DEDD NM_004216.2 IOH14789 O75618 1335,77 1492,74
Ataxin-7-like protein 3 DKFZp761G2113 XM_375456.2 IOH43380 Q14CW9 1333,88 1061,27
Uncharacterized protein C6orf201 C6orf201 NM_206834.1 IOH40081 Q7Z4U5 1320,72 1843,81
ankyrin repeat and sterile alpha motif domain containing 6 (ANKS6) ANKS6 BC064367.1 IOH39904 Q68DC2 1313,67 704,43
PREDICTED: Homo sapiens hypothetical gene supported by NM_153241 (LOC442774) MGC42157 XM_499573.1 IOH22041 NA 1303,04 1354,58
AE binding protein 2 (AEBP2) AEBP2 NM_153207.2 IOH14301 Q96BG3 1299,74 1361,00
TRAF3-interacting protein 1 TRAF3IP1 BC059174.1 IOH28851 Q8TDR0 1298,92 1990,92
leucine rich repeat containing 8 family, member D (LRRC8D) LRRC8D BC009486.1 IOH22946 Q7L1W4 1284,92 2688,00
TBP-like 1 (TBPL1) TBPL1 BC000381.2 IOH3454 P62380 1276,34 2315,63
Kruppel-like factor 12 (KLF12) KLF12 NM_007249.3 IOH10654 Q9Y4X4 1272,22 1104,63
BC006423.1 1269,40 2013,80
kinesin family member 3A (KIF3A) KIF3A NM_007054.1 IOH26900 Q9Y496 1249,02 1975,97
histone cluster 1, H2bm (HIST1H2BM) HIST1H2BM NM_003521.2 IOH40169 Q99879 1238,03 3276,52
Disks large-associated protein 5 DLG7 BC016276.1 IOH13621 Q15398 1226,51 2127,15
pituitary tumor-transforming 2 (PTTG2) PTTG2 NM_006607.1 IOH40244 Q9UNJ6 1226,06 2417,04
eukaryotic translation initiation factor 2C, 4 (EIF2C4) EIF2C4 NM_017629.2 IOH38411 Q9HCK5 1217,51 2117,44
casein kinase 1, epsilon (CSNK1E), transcript variant 2 CSNK1E NM_001894.2 IOH21160 P49674 1215,88 1263,57
chromosome 10 open reading frame 80 (C10orf80) C10orf80 NM_001008723.1 IOH43999 Q5T655 1213,37 1154,93
apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3H (APOBEC3H) APOBEC3H BC069023.1 IOH40776 A8MV17 1204,18 2796,81
mitochondrial ribosomal protein L34 (MRPL34), nuclear gene encoding mitochondrial protein MRPL34 NM_023937.1 IOH4594 Q9BQ48 1193,89 2393,34
DEAD (Asp-Glu-Ala-Asp) box polypeptide 49 (DDX49) DDX49 NM_019070.1 IOH5264 Q9Y6V7 1193,01 656,92
olfactory receptor, family 4, subfamily D, member 6 (OR4D6) OR4D6 NM_001004708.1 IOH28245 Q8NGJ1 1190,23 1760,91
heterochromatin protein 1, binding protein 3 (HP1BP3) HP1BP3 NM_016287.2 IOH43530 Q5SSJ5 1188,24 2291,86
UPF3 regulator of nonsense transcripts homolog A (yeast) (UPF3A) UPF3A BC023569.1 IOH27860 A2A366 1185,97 863,55
DEAD (Asp-Glu-Ala-Asp) box polypeptide 55 (DDX55) DDX55 BC030020.2 IOH22410 Q8NHQ9 1183,21 1595,26
RNA-binding protein 42 MGC10433 BC031682.1 IOH22859 Q9BTD8 1176,92 1113,02
ribos