Background
The client proteins of Hsp90-Cdc37
Item | Protein name | Gene symbol | Molecular functions | Partner of PPI pair |
---|---|---|---|---|
1 | SRC | SRC | Kinase, tyrosine-protein kinase, transferase | MAP4K1, PRKCA, PRKCE, RET, TYRO3, PTK2B, CHUK, DDR2, ADRBK1, EGFR, BMX, KIT, PDGFRB, RAF1, ERBB2, IKBKB, MATK, PRKCZ, ABL1, PTK2, AXL, AR, PRKACA, CDC25C, AKT1, ITK, FYN, IGF1R, CSF1R, PRKCH, PDPK1, EPHA4, LYN, PRKD1, FGR |
2 | EGFR | EGFR | Developmental protein, host cell receptor for virus entry, kinase, receptor, tyrosine-protein kinase, transferase | MAP4K1, EPHA2, AR, LYN, PDGFRB, PRKD1, FER, SRC, PTK2B, ERBB3, MAP3K12, CDK1, YES1, ERBB2, PRKCA, IGF1R, PTK2, RIPK1, MAP3K14, CAMK2A, ERBB4, VAV3, PTK6, ADRBK1, TNK2, PRKACA, CAMK2G, MAPK14 |
3 | FYN | FYN | Developmental protein, kinase, tyrosine-protein kinase, transferase | ITK, NTRK2, RAF1, NR3C1, ZAP70, TNK2, PRKCQ, PRKCE, TYK2, PTK2B, MAP4K1, CSF1R, TYRO3, PTK2, EPHA4, SRC, CDK1, YES1, PDGFRB, ABL1, PRKCZ, MAPT, NEK8, KIT, BTK, MOS, PRKCH |
4 | Raf-1 | RAF1 | Kinase, serine/threonine-protein kinase, transferase | MAP3K1, PRKCZ, FYN, PDGFRB, AR, STK3, BRAF, SRC, KSR1, AKT1, PRKCA, JAK1, MAPK3, PRKCE, MAPK7, DMPK, PRKACA, MAP3K5, NR3C1, LCK, KSR2 |
5 | AKT1 | AKT1 | Kinase, serine/threonine-protein kinase, transferase | PDPK1, PRKCQ, PKN2, AR, CHUK, MAP3K8, RAF1, BRAF, MAP3K11, PRKCZ, IKBKB, SRC, MAPK14, CAMKK1, AKT2, IRAK1, PAK6, MAP3K5, GSK3A, CHEK1 |
6 | ERK1 | MAPK3 | Kinase, serine/threonine-protein kinase, transferase | DAPK1, RPS6KA2, RPS6KA3, RPS6KA4, MAPK14, PRKCZ, RPS6KA1, KSR2, PRKCE, LCK, RAF1, CDC25C, MAP3K14, NTRK1, LYN, NTRK3, ADRBK1, BRAF, RET |
7 | P38 | MAPK14 | Kinase, serine/threonine-protein kinase, transferase | IRAK1, DYRK1B, RPS6KA4, RPS6KA3, MAPK3, MAP3K7, CSNK2A1, TGFBR1, MAP2K6, MAP2K7, CAMKK2, AKT1, RPS6KA5, CDC25C, PKN1, ELK3, RET, EGFR |
8 | FAK1 | PTK2 | Kinase, tyrosine-protein kinase, transferase | EPHA2, LYN, BMX, RET, IGF1R, SRC, EGFR, FLT4, FYN, FGR, PDGFRB, ERBB2, YES1, LCK, PTK2B, ERBB3, RIPK1 |
9 | IKK-β | IKBKB | Kinase, serine/threonine-protein kinase, transferase | CHUK, MAP3K7, EIF2AK2, MAP3K14, MAP3K1, PRKCQ, PRKCB, MAP3K3, PRKCZ, SRC, TGFBR1, MAP3K11, AKT1, ACVR1, IRAK1, TBK1 |
10 | TGFR-1 | TGFBR1 | Kinase, receptor, serine/threonine-protein kinase, transferase | CHUK, CDK17, AMHR2, DAPK2, AURKB, TGFBR2, MAPK14, CDK14, CDK6, IKBKB, MAP3K7, TSSK1B, NEK8, ITK, ACVR1, CDK4 |
11 | LYN | LYN | Kinase, tyrosine-protein kinase, transferase | TYK2, PTK2, MATK, EGFR, KIT, CDK2, CDK1, BTK, CDK4, CSF1R, PTK2B, PRKCQ, MAPK3, MAP4K1, SRC, MAP3K3 |
12 | PKC2 | PRKCZ | Kinase, serine/threonine-protein kinase, transferase | RAF1, DAPK3, MAPK3, JAK1, PDPK1, IKBKB, SRC, PRKCQ, AKT3, AKT1, GSK3A, MAP2K5, IRAK1, BTK, FYN, PRKCA |
13 | PDK1 | PDPK1 | Activator, kinase, serine/threonine-protein kinase, transferase | PKN1, AKT1, PRKACA, PKN2, RPS6KA1, RPS6KA3, PRKCZ, PTK2B, PRKCE, SGK3, AKT2, PRKCB, SRC, SGK2, AKT3 |
14 | IKK-α | CHUK | Kinase, serine/threonine-protein kinase, transferase | MAP3K8, MAP3K7, IKBKB, TGFBR1, SRC, MAP3K14, AKT1, AKT2, IRAK1, PRKCB, EIF2AK2, MAP3K11, PRKCQ, CHEK1, MAP3K3 |
15 | MEKK7 | MAP3K7 | Kinase, serine/threonine-protein kinase, transferase | CHUK, IKBKB, MAP4K1, MAP2K7, MAPK14, MAP2K6, MAP3K5, RIPK1, NLK, TGFBR1, MAP3K14, MAP3K3, EIF2AK2, MAP4K4, IRAK1 |
16 | BTK | BTK | Kinase, tyrosine-protein kinase, transferase | PRKCQ, PRKD1, LYN, JAK1, ABL1, BMX, IRAK1, PRKCE, PRKCZ, PRKCB, HCK, FYN, KIT, ITK, PRKCA |
17 | ABL | ABL1 | DNA-binding, kinase, tyrosine-protein kinase, transferase | HCK, MAP4K1, PRKD1, SRC, NTRK1, NEK8, KIT, BTK, JAK1, ZAP70, CDK1, FYN, MAPT, UHMK1 |
18 | MEKK5 | MAP3K5 | Kinase, serine/threonine-protein kinase, transferase | MAP2K7, EIF2AK2, MAP3K6, MAP3K7, MAP2K6, MAP3K2, MAP3K3, PRKAA2, RAF1, ERN1, AKT1, IGF1R, ALK |
19 | LCK | LCK | Kinase, tyrosine-protein kinase, transferase | PRKCA, ZAP70, ITK, PRKCQ, MAPK3, KIT, CDC25C, PRKACA, PTK2B, AXL, PTK2, RAF1, NR3C1 |
20 | FAK2 | PTK2B | Kinase, tyrosine-protein kinase, transferase | SRC, ZAP70, EGFR, FYN, PDPK1, ERBB3, JAK1, LYN, MATK, LCK, ERBB2, PTK2, FGFR3 |
21 | PKACA | PRKACA | Kinase, serine/threonine-protein kinase, transferase | PDPK1, STK11, NR3C1, SRC, GSK3A, CAMKK2, LCK, ADRBK1, RAF1, MAP3K3, EGFR, BRAF |
22 | IRAK | IRAK1 | Kinase, serine/threonine-protein kinase, transferase | MAPK14, CHUK, IRAK3, IRAK2, PRKCZ, MAP3K7, BTK, AKT1, RIPK2, CAMKK2, IKBKB, NTRK3 |
23 | JAK1 | JAK1 | Kinase, tyrosine-protein kinase, transferase | IGF1R, PRKCZ, TYK2, RAF1, PTK2B, EIF2AK2, BTK, ABL1, PDGFRA, FES, PDGFRB, FER |
24 | CDK1 | CDK1 | Host cell receptor for virus entry, kinase, receptor, serine/threonine-protein kinase, transferase | PKMYT1, CDC25C, LYN, EGFR, CSNK2A1, AR, PRKCB, MAPT, FYN, ABL1, AURKB, TGFBR2 |
25 | PDGFR-1 | PDGFRB | Developmental protein, kinase, receptor, tyrosine-protein kinase, transferase | VAV3, RAF1, EGFR, SRC, PDGFRA, TYK2, ARAF, FYN, YES1, EIF2AK2, JAK1, PTK2 |
26 | MEKK3 | MAP3K3 | Kinase, serine/threonine-protein kinase, transferase | MAP3K2, ALK, MAP2K5, IKBKB, MAP3K7, MYLK2, MAP3K5, PRKACA, RIPK1, CHUK, LYN |
27 | CD117 | KIT | Kinase, receptor, tyrosine-protein kinase, transferase | LYN, SRC, MATK, HCK, YES1, LCK, ABL1, FYN, BTK, PRKCA, PRKCB |
28 | AR | AR | Activator, DNA-binding, receptor | PAK6, AKT1, EGFR, GTF2F1, RAF1, GSK3A, NR3C1, CDK6, SRC, CDK1, CDK9 |
29 | GSK3α | GSK3A | Kinase, serine/threonine-protein kinase, signal transduction inhibitor, transferase | PRKCA, AR, MAPT, PRKACA, PRKCZ, SGK3, MAP3K11, PRKCB, AKT1, PRKCG |
The interaction of Hsp90-Cdc37-client protein
Targeting Hsp90-Cdc37-client protein interaction to block Hsp90 chaperone machinery
Targeting Cdc37
Targeting Cdc37-client interaction
Targeting Hsp90-Cdc37 interaction
The potential approaches to disrupt the Hsp90-Cdc37-client protein interaction | Related mechanisms | References |
---|---|---|
Targeting Cdc37 | ||
siRNAs or shRNA | Silencing Cdc37 | |
Targeting Cdc37-client interaction | ||
4,5,6,7-Tetrabromobenzotriazole | CK2 inhibitors, suppressing Cdc37 phosphorylation at Ser13 site | [59] |
PP5 mutation | Suppressing Cdc37 dephosphorylation | [48] |
Vemurafenib | B-raf inhibitor. Antagonize Cdc37 interaction with kinases | [67] |
Lapatinib | EGFR/HER2 inhibitor. Antagonize Cdc37 interaction with kinases | [67] |
Targeting Hsp90-Cdc37 interaction | ||
Celastrol | Blocking the critical interaction of Hsp90 at Glu33 and Cdc37 at Arg167 | |
Sulforaphane | Disrupting the formation of Hsp90-Cdc37 complex by direct modification of specific amino acids residues of Hsp90 | [70] |
FW-04-804 | Binding sites at Gln133 and Glu47/Arg46 of Hsp90 | |
Withaferin A | Blocking several H-bond between Hsp90-Cdc37 interaction, like Ser113 (Hsp90)-Gln208 (Cdc37) bond and Gln133 (Hsp90)-Arg166 (Cdc37) bond | |
Kongensin A | Covalently binds to a cysteine 420 in the middle domain of Hsp90 and dissociates Hsp90 from Cdc37 | |
Platycodin D | H-bond connection with Hsp90 at Arg32 and Phe200 and Cdc37 at Asp169 and Asp170 | |
Pep-1 | Cdc37-derived peptides, bound to Hsp90 N-terminal domain and inhibited Hsp90 ATPase activity | [80] |