Apoptosis Induction byHistone Deacetylase Inhibitors in Cancer Cells: Role of Ku70
Abstract
1. Introduction
2. Classification of HDACs and Cellular Location
3. Biological Functions of HDACs
4. HDACi for Cancer Therapy
5. Apoptosis Induction by HDACis
6. Ku70 Regulates Apoptosis-Related Proteins
6.1. Bax
6.2. Mcl-1
6.3. c-FLIP
7. Ku70 Acetylation by HDACi Treatment
8. Summary
Author Contributions
Funding
Conflicts of Interest
References
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Substrate | HDACs | Function of Acetylation | Reference |
---|---|---|---|
p53 | HDAC1, 2, 3, 6, SIRT1, 2, 7 | Increases transcription activity | [33,34,35,36] |
NF-κB | HDAC3, SIRT1, 2 | Impacts NF-κB translocation and NF-κB-mediated inflammation and transcription | [39,40,59,60] |
Hsp90 | HDAC3, 6 | Promotes chaperone protein degradation | [49,50,51] |
STATs | HDAC3 | Inhibits JAK2/STAT pathway and NF-kB-mediated inflammatory response | [54,61] |
Akt | HDAC3, 6, SIRT1, 2 | Decreases Akt phosphorylation and inhibits Akt-mediated pathway | [55,56,57,58] |
Ku70 | HDAC1, 3, 6, SIRT1, 3, 6 | Enhances DNA damage and reduces the stability of Ku70-regulated proteins | [62,63,64,65,66,67] |
α-tubulin | HDAC6, SIRT2 | Inhibits microtubule assembly and cell motility | [68,69] |
c-Myc | HDAC3, 6 | Inhibits the transcription ability and decreases c-Myc expression | [70,71] |
E2F1 | HDAC1 | Increases DNA-binding affinity | [72] |
HIF-1α | HDAC2, 4, 5, 7 | Regulates its degradation | [73,74,75,76] |
ER | HDAC1 | Increases cell proliferation | [77] |
β-catenin | HDAC6 | Inhibits its nuclear translocation | [78] |
GATAs | HDAC3, 4, 5 | Affects erythroid differentiation | [79,80] |
FoxOs | SIRT1 | Decreases DNA-binding affinity and reduces transcription activity | [81] |
HDAC Inhibitor | Chemical Class | Structure of the Compound | HDAC Class Inhibited |
---|---|---|---|
Vorinostat (SAHA) | Hydroxamic acid | Pan-HDACs | |
Romidepsin (FK228) | Cyclic peptide | Class I | |
Belinostat (PXD-101) | Hydroxamic acid | Pan-HDACs | |
Panobinostat (LBH-589) | Hydroxamic acid | Pan-HDACs | |
Chidamide | Benzamide | Class I, HDAC10 |
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Gong, P.; Wang, Y.; Jing, Y. Apoptosis Induction byHistone Deacetylase Inhibitors in Cancer Cells: Role of Ku70. Int. J. Mol. Sci. 2019, 20, 1601. https://doi.org/10.3390/ijms20071601
Gong P, Wang Y, Jing Y. Apoptosis Induction byHistone Deacetylase Inhibitors in Cancer Cells: Role of Ku70. International Journal of Molecular Sciences. 2019; 20(7):1601. https://doi.org/10.3390/ijms20071601
Chicago/Turabian StyleGong, Ping, Yuetong Wang, and Yongkui Jing. 2019. "Apoptosis Induction byHistone Deacetylase Inhibitors in Cancer Cells: Role of Ku70" International Journal of Molecular Sciences 20, no. 7: 1601. https://doi.org/10.3390/ijms20071601
APA StyleGong, P., Wang, Y., & Jing, Y. (2019). Apoptosis Induction byHistone Deacetylase Inhibitors in Cancer Cells: Role of Ku70. International Journal of Molecular Sciences, 20(7), 1601. https://doi.org/10.3390/ijms20071601