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Table 1 Survivin incoming signal networka: molecules that regulate survivin (drugs’ effects on survivin not included)

From: Cancer therapeutics using survivin BIRC5 as a target: what can we do after over two decades of study?

Mechanism and Effects

Classified Factors/Molecules

1. Binding to survivin for activation

Binding protein: Beclin 1, CDCA8, CUGBP1, DBC1, ELAVL1 (HuR), FAT10, HBXIP, HSP60, HSP90, MKLP2, NET1 (TSPAN1), VIL2 (ezrin). Protein: C6orf176; Enzyme: cIF2C2 (Argonaute-2), PARP6, RecQL4, SFRS1 (SF2). Regulator: Evi5. Protease: UFD1.

2. Phosphorylation of survivin for activation

Kinase: Aurora-B, Casein Kinase II alpha chains, CDK1 (p34), PLK1.

3. Deubiquitination of survivin for activation

Enzyme: JAB1.

4. Transportation of survivin for activation

Transporter: CRM1.

5. Transcriptional upregulation of survivin for activation

Transcription factor: AR, b-Myb, c-Myb, c-Myc, CREB1, DEC1 (stra13), E2F1, E2F3, EPAS1, ESR1, FBI-1(Pokemon), FOXM1, GATA-1, HIF-1, HIF1A, JunB, KLF5, Lef-1, N-Myc, NF-κB, NF-κB p50/p65, NUR77, PPAR-γ, RBP-Jκ (CBF1), NF-κB Rel A/p65, NF-κB Rel B, RUNX2, SOX2, SOX4, SP1, SP3, STAT1, STAT3, TBX5, Tcf (Lef), TCF7L2 (TCF4), TEF-1, TEF-4, TFAM, THAP1, ZFX, EBNA1 (HHV4), NOTCH1 (NICD). Binding protein: β-arrestin1, β-catenin, LIN-9, MBD3, YAP1 (Yap65,). Enzyme: CBP, HDAC3, LSD1, WHSC1. Protein: LANA (HHV8).

6. Influence on survivin expression for activation

Kinase: AKT2, JNK (MAPK8-10). Receptor ligand: Angiopoietin1, Angiopoietin 2, Angiotensin II, Apo-2L (TNFSF10), BMP6, BMP7, CCL2, Choriogonadotropin, CTGF, EGF, Epo, FGF10, FGF19, FGF2, FLT3 ligand, FSH, G-CSF, Gastrin 17-Gly, GM-CSF, HDGF, IFN-γ, IGF-1, IL-1α, IL-2, IL-22, IL-3, IL-33, IL-5, Jagged1, Leptin, MGF, TGF-β, Thrombopoietin, TNF-α, VEGF-A, WNT3A. Transcription factor: ARNT, FOXK1, HoxC10, ID1, NANOG, SIP1 (ZFHX1B), SNAIL1, SP4, STAT5A, STAT5B, TCF8. Receptor: CD44, RAGE. Binding protein: COMP, CRP, Galetin-3, Mucin 16. Receptor kinase: ErbB2, TIE2. Receptor: FN14 (TNFRSF12A), FZD7, IL6RA, LMP1 (HHV4), TLR4. Protein: HCV NS5A, TCR α/β.

7. Binding to survivin for inhibition

Binding protein: PARC, Smac (Diablo), Ubiqutin. Enzyme: Pin1. Protein: Rhbdf2.

8. Ubiquitination of survivin for inhibition

Binding protein: FBXL7, XIAP.

9. Cleavage of survivin for inhibition

Protease: Granzyme M.

10. Transcriptional regulation of survivin for inhibition

Transcription factor: NF-κB c-Rel, CDX2, E2F4, EGR1, FKHR, FOXO3A, GCR, HNF1-α, HNF4-α, HOXA4, KLF4, p53, p63, PDEF, RUNX3, YY1. Binding protein: BMI-1, p130, p21, PML. Enzyme: DNMT1, G9a, HDAC6, Sirtuin1.

11. Effect-unspecified inhibition

Enzyme: SSAT

12. Influence on survivin expression for inhibition

Receptor ligand: Adiponectin, BMP4, DLL4, IL-1β, IL-24. Transcription factor: C/EBPδ, ESR2, IRF1, NRSF, SOX7, VDR. Receptor: CD30 (TNFRSF8), Dopamine D2 receptor, TLR3, TLR9. Receptor kinase: DR5 (TNFRSF10B,). Phosphatase: FHIT. Binding protein: RPS29, SUMO-1.

13. Competition with survivin for inhibition

Receptor kinase: RET

14. miRNA binding to survivin transcript for inhibition

miRNA: miR-130-3p, mir-138-5p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-150-5p, miR-16-5p, miR195-5p, miR-203-3p, miR-214-3p, miR-218-5p, miR-222-3p, miR-320-3p, miR-320c, miR-335-5p, miR-338-5p, miR-34a-5p, miR-3613-3p, miR-483-3p, miR-485-3p, miR-494-3p, miR-497-5p, miR-542-3p, miR-542-5p, miR-548d-3p, miR-552-3p, miR-634, miR-708-5p, miR-96-5p.

15. Homodimerization for survivin stabilization

Binding protein: survivin

16. Binding to survivin with unspecified effects

Binding protein: AIP, APG5, cIAP1, cIAP2, FMIP, GSPT1, GSPT2, INCENP, TPX2, TRAP-1. Kinase: Aurora-C, GSK3β. Enzyme: Dicer. Protein: eIF3, GAS2L3, TD-60. Receptor: HLP-DRB1. Channel: Kir3.2. Transporter: SLC5A8. Regulator: p120GAP. Phosphatase: PP1-catγ. Protein: RED. Transcription factor: SFRS10, USF2, HBV-C X protein.

17. Phosphorylation of survivin with unspecified effects

Kinase: CDK5, PRPK.

18. Deubiquitination of survivin with unspecified effects

Protease: USP9X.

19. Transcription regulation of survivin with unspecified effects

Transcription factor: AHR, AML1 (RUNX1), AP-2, AP-2α, ATF-2, E2F2, E2F5, E2F6, E2F7, E2F8, ETS1, GABP-α, HNF1-β, LMO2, MAD, Max, MTF-1, Mxi1, MYOG, NF-Y, NFAT-90, Oct-2, RARα, RARβ, STAT6, TAL1, TCF7/TCF1, TCF7L1/TCF3, ZNF143, ZNF42/MZF1, hASH1, HCF1, NRB54. Binding protein: CXXC4, ING1, ING2, Rb protein, Sin3α. Enzyme: DPY30, HDAC1, HDAC4, JMJD2A, JMJD3, p300, PLU-1, PRMT1, RBB2.

20. Influence on survivin expression with unspecified effects

Receptor ligand: TGF-beta1.

21. miRNA binding to survivin transcript with unspecified effects

miRNA: miR-1225-3p, miR-1226-3p, miR-125s-3p, miR-135a-3p, miR-17-5p, miR-182-5p, miR-192-5p, miR-199a-5p, miR-19b-3p, miR-200a-3p, miR-206-3p, miR-27a-3p, miR-31-5p, miR-3127-5p, miR-320-5p, miR-338-3p, miR-449a-5p, miR-512-5p, miR-574-3p, miR-600, miR-669d-3p, miR-762, miR-764, miR-92a-3p, miR-let-7a-5p, miR-let-7f-5p

  1. aInformation was retrieved from the GeneGo database at https://portal.genego.com/ and organized by the authors. Relevant references for individual findings can be found in the database from the corresponding molecule under the “link info”.