Understanding the Role of the Transcription Factor Sp1 in Ovarian Cancer: from Theory to Practice
Abstract
:1. Introduction
2. Genetic Makeup and Structure of Sp1
3. Regulation of Sp1
4. Role of Sp1 in the Normal Cell Cycle and OC Tumorigenesis
5. Effect of Sp1 TF in Angiogenesis and Anti-Apoptosis in OC
6. Sp1 as a Therapeutic Target in OC
7. Influence of Sp1 on Cellular Reprogramming
8. Future Perspective
9. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
OC | Ovarian cancer |
Sp1 | Specificity protein 1 |
KLF | Kruppel-like family |
TF(s) | Transcription factors |
VEGF | Vascular endothelial growth factor |
CCC | Ovarian clear cell carcinoma |
JNK1 | Jun N—terminal kinase 1 |
MAPK/ERK | mitogen-activated protein kinase//extracellular signal-regulated kinase |
MDR | Multidrug resistance |
IAP | Inhibitor of apoptosis protein |
MTA | Mithramycin A |
BCL2L1 | Bcl-2-like 1 |
hTERT | Human telomerase Reverse Transcriptase |
CLDN4 | Claudin 4 |
HIFs | Hypoxia—Inducible Factors |
LCFA | Long Chain Fatty Acid |
HBXIP | Hepatitis B X—interacting protein |
Skp2 | S—phase kinase—associated protein 2 |
ROS | Reactive Oxygen Species |
NO | Nitric Oxide |
Raf | Rapidly Accelerated Fibrosarcoma |
Sox2 | SRY-Box Transcription Factor 2 |
Oct4 | Octamer-binding transcription factor 4 |
Klf4 | Kruppel-like factor 4 |
JNK1 | c-Jun N-terminal kinases |
HBXIP | Hepatitis B X-interacting protein |
CLDN | Claudin |
VEGF | Vascular endothelial growth factor |
ODC | Ornithine decarboxylase |
CDK | Cyclin-dependent protein kinases |
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# | Compound Name | Binding Site | Reactions | References |
---|---|---|---|---|
1 | Mithramycin A | Sp1 gene promoters | Alters Sp1 and DNA interactions | [64,65,66,67] |
2 | Daunorubicin | Binds to DNA with higher affinity | Inhibits Sp1-DNA interactions & gene transcription | [68,69,70] |
3 | WP631(bis-intercalating anthracycline) | Binds to DNA with higher affinity | Efficient inhibitor for transcription initiation of Sp1 containing binding sites & Sp1—activated transcription | [69,71] |
4 | Doxorubicin | Activates promoter of Cdc25B | Inhibits Sp1 binding & increases NF-Y binding to promoter and keeps P53 alive | [72] |
5 | Hedamycin | Down—regulates surviving expression | Abolishes Sp1 binding to putative binding elements & modulates viability of cancer cells | [73] |
6 | Elsamicin A | DNA—protein interactions in c–myc promoters | Affects Sp1 binding in a dose—dependent manner | [74] |
7 | Actinomycin D | DNA—protein interactions | Sp1 TFs induce TNF expressions on angiogenic factors in cancer cells | [75] |
8 | Tolfenamic acid | Drug—DNA interaction | Increases ubiquitination of Sp1 as well as the proteasome–dependent degradation (downregulates Sp1) | [76,77] |
9 | Aspirin | Cells that response to sequestration of zinc ions | It induces caspase–dependent cleavage of Sp1 protein factors | [78] |
10 | Arsenic trioxide | Human telomerase reverse transcriptase (hTERT) gene | Suppresses transcription of hTERT gene through regulation Sp1 TF | [79] |
11 | Curcumin (diferuloylmethane) | Not described | Induces proteasome–dependent down—regulation of Sp1 proteins | [80,81] |
12 | Betulinic acid | Not described | Decreases expression of Sp1 TF in cancer cells | [82] |
13 | Resveratrol (3,5,4′-trihydroxy-trans-stilbene) | Not described | Inhibits cell growth and Sp1 TF directly | [83] |
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Vellingiri, B.; Iyer, M.; Devi Subramaniam, M.; Jayaramayya, K.; Siama, Z.; Giridharan, B.; Narayanasamy, A.; Abdal Dayem, A.; Cho, S.-G. Understanding the Role of the Transcription Factor Sp1 in Ovarian Cancer: from Theory to Practice. Int. J. Mol. Sci. 2020, 21, 1153. https://doi.org/10.3390/ijms21031153
Vellingiri B, Iyer M, Devi Subramaniam M, Jayaramayya K, Siama Z, Giridharan B, Narayanasamy A, Abdal Dayem A, Cho S-G. Understanding the Role of the Transcription Factor Sp1 in Ovarian Cancer: from Theory to Practice. International Journal of Molecular Sciences. 2020; 21(3):1153. https://doi.org/10.3390/ijms21031153
Chicago/Turabian StyleVellingiri, Balachandar, Mahalaxmi Iyer, Mohana Devi Subramaniam, Kaavya Jayaramayya, Zothan Siama, Bupesh Giridharan, Arul Narayanasamy, Ahmed Abdal Dayem, and Ssang-Goo Cho. 2020. "Understanding the Role of the Transcription Factor Sp1 in Ovarian Cancer: from Theory to Practice" International Journal of Molecular Sciences 21, no. 3: 1153. https://doi.org/10.3390/ijms21031153