| Name | Cyclic AMP-dependent transcription factor ATF-4 | ||
| UniProt ID | ATF4_HUMAN | ||
| Gene Name | ATF4 | ||
| Gene ID | 468 | ||
| Synonyms |
ATF4, CREB-2, CREB2, TAXREB67, TXREB
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| Sequence |
MTEMSFLSSEVLVGDLMSPFDQSGLGAEESLGLLDDYLEVAKHFKPHGFSSDKAKAGSSE
WLAVDGLVSPSNNSKEDAFSGTDWMLEKMDLKEFDLDALLGIDDLETMPDDLLTTLDDTC DLFAPLVQETNKQPPQTVNPIGHLPESLTKPDQVAPFTFLQPLPLSPGVLSSTPDHSFSL ELGSEVDITEGDRKPDYTAYVAMIPQCIKEEDTPSDNDSGICMSPESYLGSPQHSPSTRG SPNRSLPSPGVLCGSARPKPYDPPGEKMVAAKVKGEKLDKKLKKMEQNKTAATRYRQKKR AEQEALTGECKELEKKNEALKERADSLAKEIQYLKDLIEEVRKARGKKRVP |
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| Pathway Map | MAP LINK | ||
| T.C. Number | 8.A.23.1.57 | ||
| KEGG ID | hsa468 | ||
| TTD ID | T53270 | ||
| Pfam | PF00170; PF03131; PF06009; PF07716; PF07767; PF11932; PF13166; PF13830; PF14362 | ||
| Pair Name | Anacardic Acid, Bortezomib | |||
| Phytochemical | Anacardic Acid | |||
| Drug | Bortezomib | |||
| Disease Info | [ICD-11: 2A83] | Multiple myeloma | Investigative | |
| Regulate Info | Up-regulation | Cyclic AMP-dependent transcription factor ATF-4 | Expression | |
| Result | The results of the present study suggest that AA/Bor combination may be a potential therapeutic strategy for MM treatment. | |||
| Pair Name | Decursin, TNF-related apoptosis inducing ligand | |||
| Phytochemical | Decursin | |||
| Drug | TNF-related apoptosis inducing ligand | |||
| Disease Info | [ICD-11: 2C25] | Lung cancer | Investigative | |
| Regulate Info | Up-regulation | Cyclic AMP-dependent transcription factor ATF-4 | Activity | |
| Result | ROS generation by decursin selectively activated the PERK/ATF4 axis of the endoplasmic reticulum stress signalling pathway, leading to enhanced TRAIL sensitivity in TRAIL-resistant NSCLC cell lines, partly via up-regulation of DR5. | |||
| Pair Name | Dihydroartemisinin, Oxaliplatin | |||
| Phytochemical | Dihydroartemisinin | |||
| Drug | Oxaliplatin | |||
| Disease Info | [ICD-11: 2B91] | Colorectal cancer | Investigative | |
| Regulate Info | Up-regulation | Cyclic AMP-dependent transcription factor ATF-4 | Expression | |
| Result | We demonstrated an improved therapeutic strategy for CRC patients by combining DHA and oxaliplatin treatments. | |||
| Pair Name | Piperlongumine, Bortezomib | |||
| Phytochemical | Piperlongumine | |||
| Drug | Bortezomib | |||
| Disease Info | [ICD-11: 2C12] | Hepatocellular carcinoma | Investigative | |
| Regulate Info | Up-regulation | Cyclic AMP-dependent transcription factor ATF-4 | Expression | |
| Result | Piperlongumine and bortezomib synergically inhibit cholangiocarcinoma via ER stress-induced cell death | |||
| Pair Name | Piperlongumine, HSP90 inhibitors | |||
| Phytochemical | Piperlongumine | |||
| Drug | HSP90 inhibitors | |||
| Disease Info | [ICD-11: 2B90] | Colon cancer | Investigative | |
| Regulate Info | Up-regulation | Cyclic AMP-dependent transcription factor ATF-4 | Expression | |
| Result | Combination therapy with HSP90 inhibitors and piperlongumine promotes ROS-mediated ER stress in colon cancer cells | |||
| Pair Name | Resveratrol, Cisplatin | |||
| Phytochemical | Resveratrol | |||
| Drug | Cisplatin | |||
| Disease Info | [ICD-11: 2B72] | Gastric cancer | Investigative | |
| Regulate Info | Up-regulation | Cyclic AMP-dependent transcription factor ATF-4 | Activity | |
| Result | These results indicated that RES is a promising adjuvant for DDP during GC chemotherapy. | |||
| Pair Name | Shikonin, Osimertinib | |||
| Phytochemical | Shikonin | |||
| Drug | Osimertinib | |||
| Disease Info | [ICD-11: 2C25] | Lung cancer | Investigative | |
| Regulate Info | Up-regulation | Cyclic AMP-dependent transcription factor ATF-4 | Expression | |
| Result | Shikonin increased the anticancer activity of AZD9291 in primary wtEGFR NSCLC cells through ROS-mediated ER stress | |||
| Pair Name | Shogaol, Gefitinib | |||
| Phytochemical | Shogaol | |||
| Drug | Gefitinib | |||
| Disease Info | [ICD-11: 2C73] | Ovarian Cancer | Investigative | |
| Regulate Info | Up-regulation | Cyclic AMP-dependent transcription factor ATF-4 | Expression | |
| Result | Our results suggest that 6-shogaol exerts a potential anti-cancer effect in ovarian cancer and combination treatment with 6-shogaol and gefitinib may provide a novel anti-tumor therapeutic strategy in gefitinib-resistant ovarian cancer. | |||
| Pair Name | Tannic acid, Cisplatin | |||
| Phytochemical | Tannic acid | |||
| Drug | Cisplatin | |||
| Disease Info | [ICD-11: 2C25] | Lung cancer | Investigative | |
| Regulate Info | Up-regulation | Cyclic AMP-dependent transcription factor ATF-4 | Expression | |
| Result | The combination of TA and CDDP may produce synergistic antitumoral effects mediated by the PERK-ATF4-CHOP apoptotic axis, suggesting a novel adjuvant treatment for lung cancer. | |||
| Pair Name | Ursodiol, Bortezomib | |||
| Phytochemical | Ursodiol | |||
| Drug | Bortezomib | |||
| Disease Info | [ICD-11: 2A00] | Glioblastoma multiforme | Investigative | |
| Regulate Info | Up-regulation | Cyclic AMP-dependent transcription factor ATF-4 | Expression | |
| Result | Ursodeoxycholic Acid Inhibits Glioblastoma Progression via Endoplasmic Reticulum Stress Related Apoptosis and Synergizes with the Proteasome Inhibitor Bortezomib | |||
| Pair Name | Withaferin A, Fluorouracil | |||
| Phytochemical | Withaferin A | |||
| Drug | Fluorouracil | |||
| Disease Info | [ICD-11: 2B91] | Colorectal cancer | Investigative | |
| Regulate Info | Up-regulation | Cyclic AMP-dependent transcription factor ATF-4 | Expression | |
| Result | Synergistic antitumor effect of 5-fluorouracil and withaferin-A induces endoplasmic reticulum stress-mediated autophagy and apoptosis in colorectal cancer cells | |||
| Pair Name | Zerumbone, Celecoxib | |||
| Phytochemical | Zerumbone | |||
| Drug | Celecoxib | |||
| Disease Info | [ICD-11: 2B90] | Colon cancer | Investigative | |
| Regulate Info | Up-regulation | Cyclic AMP-dependent transcription factor ATF-4 | Expression | |
| Result | Our results provide novel insights into the role of ATF3 as an essential transcription factor for p53-independent DR5 induction upon both ZER and CCB treatment, and this may be a useful biomarker for TRAIL-based anticancer therapy. | |||
| Pair Name | Honokiol, Paclitaxel | |||
| Phytochemical | Honokiol | |||
| Drug | Paclitaxel | |||
| Disease Info | [ICD-11: 2C25] | Lung cancer | Investigative | |
| Regulate Info | Up-regulation | Cyclic AMP-dependent transcription factor ATF-4 | Expression | |
| Result | Synergistic killing effect of paclitaxel and honokiol in non-small cell lung cancer cells through paraptosis induction | |||
| No. | Title | Href |
|---|---|---|
| 1 | Combined therapeutic effects of bortezomib and anacardic acid on multiple myeloma cells via activation of the endoplasmic reticulum stress response. Mol Med Rep. 2016 Sep;14(3):2679-84. doi: 10.3892/mmr.2016.5533. | Click |
| 2 | Decursin enhances TRAIL-induced apoptosis through oxidative stress mediated- endoplasmic reticulum stress signalling in non-small cell lung cancers. Br J Pharmacol. 2016 Mar;173(6):1033-44. doi: 10.1111/bph.13408. | Click |
| 3 | Dihydroartemisinin enhances the anti-tumor activity of oxaliplatin in colorectal cancer cells by altering PRDX2-reactive oxygen species-mediated multiple signaling pathways. Phytomedicine. 2022 Apr;98:153932. doi: 10.1016/j.phymed.2022.153932. | Click |
| 4 | Piperlongumine and bortezomib synergically inhibit cholangiocarcinoma via ER stress-induced cell death. Naunyn Schmiedebergs Arch Pharmacol. 2023 Jan;396(1):109-120. doi: 10.1007/s00210-022-02305-4. | Click |
| 5 | Combination therapy with HSP90 inhibitors and piperlongumine promotes ROS-mediated ER stress in colon cancer cells. Cell Death Discov. 2023 Oct 13;9(1):375. doi: 10.1038/s41420-023-01672-y. | Click |
| 6 | Resveratrol synergizes with cisplatin in antineoplastic effects against AGS gastric cancer cells by inducing endoplasmic reticulum stress‑mediated apoptosis and G2/M phase arrest. Oncol Rep. 2020 Oct;44(4):1605-1615. doi: 10.3892/or.2020.7708. | Click |
| 7 | A natural anthraquinone derivative shikonin synergizes with AZD9291 against wtEGFR NSCLC cells through reactive oxygen species-mediated endoplasmic reticulum stress. Phytomedicine. 2020 Mar;68:153189. doi: 10.1016/j.phymed.2020.153189. | Click |
| 8 | 6-Shogaol Overcomes Gefitinib Resistance via ER Stress in Ovarian Cancer Cells. Int J Mol Sci. 2023 Jan 30;24(3):2639. doi: 10.3390/ijms24032639. | Click |
| 9 | Synergistic anticancer activity of cisplatin combined with tannic acid enhances apoptosis in lung cancer through the PERK-ATF4 pathway. Eur J Med Res. 2023 Oct 27;28(1):462. doi: 10.1186/s40001-023-01420-z. | Click |
| 10 | Ursodeoxycholic Acid Inhibits Glioblastoma Progression via Endoplasmic Reticulum Stress Related Apoptosis and Synergizes with the Proteasome Inhibitor Bortezomib. ACS Chem Neurosci. 2020 May 6;11(9):1337-1346. doi: 10.1021/acschemneuro.0c00095. | Click |
| 11 | Synergistic antitumor effect of 5-fluorouracil and withaferin-A induces endoplasmic reticulum stress-mediated autophagy and apoptosis in colorectal cancer cells. Am J Cancer Res. 2020 Mar 1;10(3):799-815. | Click |
| 12 | Role of activating transcription factor 3 (ATF3) in endoplasmic reticulum (ER) stress-induced sensitization of p53-deficient human colon cancer cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis through up-regulation of death receptor 5 (DR5) by zerumbone and celecoxib. J Biol Chem. 2014 Aug 1;289(31):21544-61. doi: 10.1074/jbc.M114.558890. | Click |
| 13 | Synergistic killing effect of paclitaxel and honokiol in non-small cell lung cancer cells through paraptosis induction. Cell Oncol (Dordr). 2021 Feb;44(1):135-150. doi: 10.1007/s13402-020-00557-x. | Click |
