Table 3.
Alterations in the levels of the proteins associated with cell death in bladder carcinoma 5637 cells in response to treatment with the heat shock protein 90 inhibitors AUY922 and ganetespib (STA9090).
| Accession no. | Protein description | Symbol | Protein function | Protein level (ppm) | ||
|---|---|---|---|---|---|---|
| Untreated | AUY922 | STA9090 | ||||
| Regulation of Cell Cycle | ||||||
| 5921731 | G2/mitotic-specific cyclin-B2 | CCNB2 | Cyclin | 7.83 | 0 | 0 |
| 166214910 | Cyclin-C | CCNC | Cyclin | 22.01 | 0 | 0 |
| 1706232 | Cyclin-H | CCNH | Cyclin | 28.93 | 0 | 0 |
| 218511966 | Cyclin-K | CCNK | Cyclin | 37.59 | 0 | 6.13 |
| 74753368 | Cyclin-L1 | CCNL1 | Cyclin | 11.84 | 5.99 | 3.78 |
| 9296942 | Cyclin-T1 | CCNT1 | Cyclin | 12.87 | 0 | 0 |
| 334302921 | Cyclin-dependent kinase 1 | CDK1 | CDK | 293.60 | 169.77 | 167.49 |
| 116051 | Cyclin-dependent kinase 2 | CDK2 | CDK | 177.66 | 105.75 | 95.39 |
| 231726 | Cyclin-dependent kinase 3 | CDK3 | CDK | 132.74 | 82.66 | 69.90 |
| 1168867 | Cyclin-dependent kinase 4 | CDK4 | CDK | 174.73 | 62.40 | 58.64 |
| 4033704 | Cyclin-dependent kinase 5 | CDK5 | CDK | 170.65 | 86.34 | 109.52 |
| 266423 | Cyclin-dependent kinase 6 | CDK6 | CDK | 152.85 | 77.33 | 119.90 |
| 68067660 | Cyclin-dependent kinase 9 | CDK9 | CDK | 167.44 | 59.30 | 85.97 |
| 6226784 | Cyclin-dependent kinase 10 | CDK10 | CDK | 25.95 | 0 | 0 |
| 34978359 | Cyclin-dependent kinase 11B | CDK11B | CDK | 66.60 | 19.82 | 26.82 |
| 308153421 | Cyclin-dependent kinase 12 | CDK12 | CDK | 27.17 | 10.58 | 16.69 |
| 66774048 | Cyclin-dependent kinase 13 | CDK13 | CDK | 28.84 | 10.42 | 9.40 |
| 266425 | Cyclin-dependent kinase 16 | CDK16 | CDK | 81.63 | 31.77 | 28.66 |
| 17375734 | Cyclin-G-associated kinase | GAK | CDK | 2.38 | 2.40 | 0 |
| 205371737 | Anaphase-promoting complex subunit 4 | APC4 | Mitosis factor | 15.42 | 0 | 0 |
| 37537861 | Anaphase-promoting complex subunit 5 | APC5 | Mitosis factor | 4.13 | 0 | 0 |
| 294862527 | Anaphase-promoting complex subunit 7 | APC7 | Mitosis factor | 20.80 | 0 | 5.93 |
| 34395509 | Anaphase-promoting complex subunit 10 | APC10 | Mitosis factor | 67.34 | 0 | 0 |
| 37537763 | Cell division cycle protein 16 homolog | CDC16 | Mitosis factor | 20.09 | 0 | 11.46 |
| 254763423 | Cell division cycle protein 23 homolog | CDC23 | Mitosis factor | 15.65 | 0 | 0 |
| 12644198 | Cell division cycle protein 27 homolog | CDC27 | Mitosis factor | 7.56 | 0 | 0 |
| 52783153 | Mitotic spindle assembly checkpoint protein MAD1 | MD1L1 | Mitosis factor | 17.35 | 17.56 | 4.95 |
| 384872321 | Cyclin-dependent kinase inhibitor 2A | CD2A2 | CDK inhibitor | 1038.10 | 2530.58 | 2611.11 |
| 19863257 | Cullin-1 | CUL1 | Positive regulator | 24.08 | 0 | 4.58 |
| 1709658 | Serine/threonine-protein kinase PLK1 | PLK1 | Positive regulator | 30.99 | 15.68 | 6.48 |
| 19858646 | DNA replication licensing factor MCM5 | MCM5 | Positive regulator | 67.89 | 30.05 | 62.93 |
| 2497824 | DNA replication licensing factor MCM6 | MCM6 | Positive regulator | 79.66 | 72.93 | 69.25 |
| 20981696 | DNA replication licensing factor MCM7 | MCM7 | Positive regulator | 99.62 | 78.89 | 84.01 |
| 76803807 | Origin recognition complex subunit 1 | ORC1 | Positive regulator | 7.23 | 3.66 | 0 |
| 8488999 | Origin recognition complex subunit 2 | ORC2 | Positive regulator | 16.19 | 5.46 | 0 |
| 8928268 | Origin recognition complex subunit 3 | ORC3 | Positive regulator | 4.38 | 0 | 4.99 |
| 6174924 | Origin recognition complex subunit 5 | ORC5 | Positive regulator | 21.48 | 21.73 | 16.34 |
| 25091097 | Double-strand-break repair protein rad21 homolog | RAD21 | Positive regulator | 167.81 | 134.84 | 129.52 |
| 13633914 | Mothers against decapentaplegic homolog 2 | SMAD2 | Positive regulator | 13.34 | 6.75 | 5.22 |
| 51338669 | Mothers against decapentaplegic homolog 3 | SMAD3 | Positive regulator | 51.29 | 29.66 | 41.80 |
| 135674 | Transforming growth factor β-1 | TGFB1 | Positive regulator | 23.96 | 16.16 | 0 |
| 132164 | Retinoblastoma-associated protein | RB | Positive regulator | 3.36 | 0 | 0 |
| 20455502 | Glycogen synthase kinase-3 β | GSK3B | Negative regulator | 14.83 | 15.01 | 16.92 |
| 1345590 | 14-3-3 protein β/α | YWHAB | Negative regulator | 468.41 | 640.51 | 606.65 |
| 1345593 | 14-3-3 protein η | YWHAH | Negative regulator | 215.22 | 333.06 | 375.55 |
| 48428721 | 14-3-3 protein γ | YWHAG | Negative regulator | 428.69 | 535.85 | 517.88 |
| 112690 | 14-3-3 protein θ | YWHAQ | Negative regulator | 483.03 | 565.95 | 522.11 |
| 52000887 | 14-3-3 protein ζ/δ | YWHAZ | Negative regulator | 699.13 | 771.74 | 696.15 |
| Regulation of Apoptosis | ||||||
| 18202042 | Bcl-2-like protein 11 | B2L11 | Pro-apoptosis | 0 | 15.92 | 0 |
| 23396740 | Bcl-2-like protein 13 | B2L13 | Pro-apoptosis | 12.84 | 0 | 36.63 |
| 728945 | Apoptosis regulator BAX | BAX | Pro-apoptosis | 97.32 | 131.30 | 174.03 |
| 2493274 | Bcl-2 homologous antagonist/killer | BAK | Pro-apoptosis | 29.52 | 44.81 | 33.68 |
| 33860140 | Apoptosis-stimulating of p53 protein 2 | ASPP2 | Pro-apoptosis | 0 | 0 | 3.15 |
| 6685617 | Mitogen-activated protein kinase kinase kinase 5 | MAP3K5 | Pro-apoptosis | 0 | 4.59 | 0 |
| 13431764 | Apoptosis-inducing factor 1, mitochondrial | AIFM1 | Pro-apoptosis | 246.76 | 259.10 | 301.42 |
| 74752283 | Apoptosis-inducing factor 2, mitochondrial | AIFM2 | Pro-apoptosis | 8.35 | 33.79 | 28.58 |
| 125987821 | Dynamin-1-like protein | DNM1L | Pro-apoptosis | 21.16 | 0 | 28.97 |
| 150417955 | Serine/threonine-protein phosphatase PGAM5 | PGAM5 | Necroptosis | 560.36 | 665.15 | 725.41 |
| 12231007 | Caspase-14 | CASPE | Caspase | 12.87 | 78.13 | 73.41 |
| 115612 | Calpain small subunit 1 | CPNS1 | Calpain-calcium | 81.34 | 94.07 | 79.55 |
| 317373596 | Calpain-2 catalytic subunit | CAN2 | Calpain-calcium | 63.03 | 71.18 | 101.52 |
| 33112239 | Calpain-7 | CAN7 | Calpain-calcium | 0 | 3.88 | 0 |
| 57012667 | Anamorsin | CPIN1 | Pro-survival | 9.98 | 0 | 11.38 |
| 126302556 | Calpastatin | ICAL | Pro-survival | 8.80 | 0 | 0 |
| 124297 | Interleukin-1α | IL1A | Pro-survival | 22.98 | 0 | 0 |
| 62906858 | Interleukin-1β | IL1B | Pro-survival | 46.31 | 0 | 0 |
| 125987833 | Interleukin-1 receptor-associated kinase-like 2 | IRAK2 | Pro-survival | 14.95 | 0 | 0 |
| 18202671 | Myeloid differentiation primary response protein MyD88 | MYD88 | Pro-survival | 10.52 | 0 | 0 |
| 21542418 | Nuclear factor NF-κ-B p105 subunit | NFKB1 | Pro-survival | 9.65 | 6.51 | 3.67 |
| 125198 | cAMP-dependent protein kinase type II-α regulatory subunit | PRKAR2A | Pro-survival | 92.50 | 62.40 | 87.95 |
| 62906901 | Transcription factor p65 | RELA | Pro-survival | 16.96 | 11.43 | 12.89 |
| Regulation of DNA Damage Repair | ||||||
| 73921676 | DNA-(apurinic or apyrimidinic site) lyase 2 | APEX2 | Base excision repair | 12.02 | 0 | 0 |
| 37999897 | Uracil-DNA glycosylase | UNG | Base excision repair | 29.85 | 20.13 | 22.70 |
| 206729922 | DNA-3-methyladenine glycosylase | MPG | Base excision repair | 20.90 | 0 | 0 |
| 251757259 | DNA ligase 3 | LIG3 | Base excision repair | 37.04 | 31.23 | 4.22 |
| 317373290 | DNA repair protein XRCC1 | XRCC1 | Base excision repair | 49.20 | 0 | 22.45 |
| 50401132 | Bifunctional polynucleotide phosphatase/kinase | PNKP | Base excision repair | 23.91 | 12.09 | 27.28 |
| 17380230 | Poly [ADP-ribose] polymerase 2 | PARP2 | Base excision repair | 26.71 | 16.21 | 24.37 |
| 123369 | High mobility group protein B1 | HMGB1 | Base excision repair | 506.98 | 381.08 | 214.84 |
| 296453081 | DNA repair protein complementing XP-C cells | XPC | Nucleotide excision repair | 3.31 | 0 | 3.78 |
| 12643730 | DNA damage-binding protein 1 | DDB1 | Nucleotide excision repair | 188.50 | 77.40 | 99.74 |
| 12230033 | DNA damage-binding protein 2 | DDB2 | Nucleotide excision repair | 29.17 | 14.76 | 33.28 |
| 119541 | TFIIH basal transcription factor complex helicase XPB subunit | ERCC3 | Nucleotide excision repair | 31.86 | 20.14 | 22.71 |
| 17380328 | General transcription factor IIH subunit 4 | GTF2H4 | Nucleotide excision repair | 74.15 | 40.92 | 30.76 |
| 1705722 | Cyclin-dependent kinase 7 | CDK7 | Nucleotide excision repair | 36.00 | 18.21 | 41.07 |
| 1706232 | Cyclin-H | CCNH | Nucleotide excision repair | 28.93 | 0 | 0 |
| 1708932 | CDK-activating kinase assembly factor MAT1 | MNAT1 | Nucleotide excision repair | 20.16 | 0 | 0 |
| 25091548 | Pre-mRNA-splicing factor SYF1 | XAB2 | Nucleotide excision repair | 87.42 | 51.60 | 45.71 |
| 108936013 | Cullin-4A | CUL4A | Nucleotide excision repair | 36.93 | 16.60 | 18.72 |
| 296439468 | Cullin-4B | CUL4B | Nucleotide excision repair | 20.47 | 0 | 7.78 |
| 1171032 | DNA mismatch repair protein Msh2 | MSH2 | Mismatch excision repair | 10.00 | 6.74 | 7.60 |
| 60392986 | DNA repair protein RAD50 | RAD50 | Homologous recombination | 71.21 | 60.04 | 67.70 |
| 17380137 | Double-strand break repair protein MRE11A | MRE11A | Homologous recombination | 39.59 | 4.45 | 20.07 |
| 74762960 | Nibrin | NBN | Homologous recombination | 41.30 | 8.35 | 18.85 |
| 116242745 | DNA endonuclease RBBP8 | RBBP8 | Homologous recombination | 3.47 | 3.51 | 0 |
| 166898077 | Crossover junction endonuclease MUS81 | MUS81 | Homologous recombination | 5.65 | 0 | 0 |
| 1705486 | Bloom syndrome protein | BLM | Homologous recombination | 4.40 | 0 | 5.01 |
| 38258929 | DNA-dependent protein kinase catalytic subunit | PRKDC | Non-homologous end-joining | 521.31 | 415.28 | 438.99 |
| 125731 | X-ray repair cross-complementing protein 5 | XRCC5 | Non-homologous end-joining | 582.87 | 439.11 | 495.12 |
| 125729 | X-ray repair cross-complementing protein 6 | XRCC6 | Non-homologous end-joining | 772.18 | 574.37 | 554.28 |
| 229462842 | Chromatin assembly factor 1 subunit A | CHAF1A | Chromatin structure and modification | 6.52 | 6.59 | 3.71 |
| 48428038 | Aprataxin | APTX | Editing and processing nuclease | 43.74 | 8.85 | 19.96 |
| 146325723 | E3 ubiquitin-protein ligase SHPRH | SHPRH | Ubiquitination and modification | 1.85 | 0 | 0 |
| 46577660 | Ubiquitin-conjugating enzyme E2 N | UBE2N | Ubiquitination and modification | 225.38 | 228.05 | 116.88 |
| 254763430 | 7,8-dihydro-8-oxoguanine Triphosphatase | NUDT1 | Modulation of nucleotide pools | 15.81 | 0 | 0 |
| 347595814 | Deoxyuridine 5′-triphosphate nucleotidohydrolase, mitochondrial | DUT | Modulation of nucleotide pools | 49.43 | 37.51 | 14.10 |
| 269849759 | Cellular tumor antigen p53 | TP53 | Other related | 55.47 | 16.03 | 36.16 |
| 8928568 | Tumor suppressor p53-binding protein 1 | TP53BP1 | Other related | 53.70 | 6.39 | 45.04 |
| 68565701 | Telomere-associated protein RIF1 | RIF1 | Other related | 51.65 | 3.82 | 45.99 |
| 1705919 | Dual specificity protein kinase CLK2 | CLK2 | Other related | 12.48 | 6.31 | 21.36 |
| 55976619 | Pre-mRNA-processing factor 19 | PRPF19 | Other related | 463.44 | 331.38 | 373.65 |
| ROS Generation | ||||||
| 134665 | Superoxide dismutase [Mn] | SODM | Antioxidant | 939.90 | 865.89 | 640.22 |
| 311033481 | Glutathione peroxidase 1 | GPX1 | Antioxidant | 230.12 | 232.85 | 87.51 |
| 269849565 | Glutathione peroxidase 8 | GPX8 | Antioxidant | 149.01 | 150.77 | 51.00 |
| 300680960 | Glutathione S-transferase θ-2 | GST2 | Antioxidant | 12.76 | 12.91 | 0 |
| 12643338 | Glutathione S-transferase κ-1 | GSTK1 | Antioxidant | 358.28 | 334.64 | 141.50 |
| 6016173 | Glutathione S-transferase ω-1 | GSTO1 | Antioxidant | 129.22 | 117.68 | 88.46 |
| 121746 | Glutathione S-transferase P | GSTP1 | Antioxidant | 177.96 | 120.04 | 67.68 |
| 14916998 | Glutathione reductase | GSHR | Reductase | 17.90 | 6.03 | 6.80 |
| 2506326 | Xanthine dehydrogenase/oxidase | XDH | Oxidase | 0 | 0 | 2.66 |
| Regulation of Autophagy | ||||||
| 20178289 | Interferon α21 | IFNA21 | Autophagy | 0 | 0 | 18.80 |
| 74730233 | Phosphatidylinositol 3-kinase, catalytic subunit type 3 | PIK3C3 | Autophagy | 0 | 10.66 | 8.01 |
| 317373311 | Phosphatidylinositol 3-kinase regulatory subunit β | PIK3R2 | Autophagy | 0 | 4.33 | 0 |
| 74762700 | Phosphoinositide 3-kinase, regulatory subunit 4 | PIK3R4 | Autophagy | 0 | 2.32 | 5.23 |
| 61212142 | Autophagy-related protein 3 | ATG3 | Autophagy | 0 | 10.04 | 0 |
| 17366828 | Autophagy-related protein 5 | ATG5 | Autophagy | 11.32 | 14.59 | 12.92 |
| 20140441 | Autophagy-related protein 13 | ATG13 | Autophagy | 0 | 0 | 6.87 |
ROS, reactive oxygen species.