1. Telomerase reverse transcriptase in the regulation of gene expression
IN THE NAME OF GOD
Telomerase reverse transcriptase in the regulation of gene
expression
BY SAEEDE GHIYASI

2. Telomer and telomerase

3. Regulates Gene Expression
TELOMERASE STRUCTURE
Canonical func
Extends Telomeres
Reverse Transcripase
TERT
Non-canonical func
Regulates Gene Expression
TELOMERASE
TERC
DNA template (RNA)

4. Telomerase is active in
the germ line
Telomerase is active in
stem cells
activated lymphocytes

5. Telomerase is reactivated in 90% of all cancers.
upregulation of telomerase activity in cancer cells promotes
cell proliferation
invasion
resistance to apoptosis
A critical step in human carcinogenicity

6. NON- CANONICAL FUNC NF-κB signaling pathway Wnt/β-catenin pathway
participates inDNA damage repair
promotes cell survival under oxidative stress

7. Ectopic Expression Of hTERT in bovine adrenocortical cells
Upregulation of 5 growth promoting genes
Ectopic Expression Of hTERT in bovine adrenocortical cells
Downregulation of 7 growth inhibitory genes

8. cell cycle regulation metabolism differentiation apoptosis
Experiments In Bovine Adrenocortical Cells With Ectopically Expressed hTERT
284 genes that were associated with
cell cycle regulation metabolism differentiation apoptosis
Altered By
hTERT Overexpression

9. hTERT regulates Mac-2BP ANALYSIS OF HUMAN FORESKIN FIBROBLAST CELLS
VEGF
hTERT regulates
cyclin D1

10. telomerase may be involved in epigenetic modifications or the
modulation of chromatin structure
hypotheses
NF-κB
interact with transcription
factors
β-catenin

11. Nf-κb Are Activated In Cancerous Cells
NF-κB activates the expression of TERT, by binding to the promoter of TERT
p65 was shown to modulate hTERT translocation from the cytoplasm to the nucleus
hTERT Directly Regulates The Expression Of The Nf-κb-dependent Genes
By binding to p65, and localizing to a subset of NF-κB promoters, such as IL-6, TNF-α and IL-8.

12. tumor progression MMP Family Cell Invasion NF-κB EMT- related genes
(vimentin and snail1)
Transformation
interacted with β-catenin
VEGF
NF-κB
Angiogenesis

13. Wnt/β-catenin signaling
cell fate decision
mutations in the Wnt pathway resulting
in tumorigenesis
Wnt/β-catenin signaling
axis formation
Organ development

14. Wnt/β-catenin signaling
Wnt signaling is turned off
Wnt signaling is turned on
form protein complexes
(APC), Axin, and β-catenin
APC-Axin-GSK3β complex is destabilized through Dsh
β-catenin accumulation
in the cytoplasm
phosphorylation
of β-catenin by CKI and GSK3β
Stabilized β-catenin enters the nucleus,
activates the transcription of downstream target
genes, in concert with the TCF/LEF
Degradation by the 26S proteasome

16. TERT Up regulated Wnt, Shh And BMP Pathway Related Genes
Bambi Bmp8a Ccnd2 Lef1 Nkd2 Smad Wnt5a Wnt11
TERT Up regulated Wnt, Shh And BMP Pathway Related Genes
TERT acts as a cofactor in the β-catenin transcription complex;
in this complex, TERT interacts with BRG1
a chromatin remodeling factor, to regulate
the Wnt/β-catenin signaling pathway

17. Failed To Verify The Physical Association Of hTERT And Wnt Pathway:
Greider’s Lab Suggested That There Were Indistinguishable Phenotypes Between The Mice Deficient In mTERT And mTR, And No Apparent Wnt Pathway Defects Were Observed In The mTERT-/- Mice.
Ghosh failed to verify the physical association of hTERT and BRG1
It is possible that the impact of TERT
on the regulation of the Wnt/β-catenin signaling pathway may
become biologically relevant, under particular physiopathological
conditions

18. TERT not only activated the Wnt/β-catenin pathway, but β-catenin could also directly regulate the transcription of TERT

19. RMRP
RMRP is a 267 nucleotide non-coding RNA that is highly expressed in many human and murine tissues. RMRP mutations are associated with Cartilage Hair Hypoplasia (CHH)
RMRP is essential for early embryonic development
hTERT could interact with the RNA component of the mitochondrial RNA-processing endoribonuclease
(RMRP), to form a ribonucleoprotein complex that has RNA-dependent RNA polymerase activity.

20. TERC IN THE REGULATION OF glycolytic pathway
8 of which are involved
in the glycolytic pathway
suppression of
mTERC
significant downregulation of 138 genes
the association of
hTERT expression with the glycolytic pathway may contribute
to the resistance of cancer cells to regulation by the tumor
microenvironment

21. some NF-κB target genes is decreased in the TERC knockout mice
suppression of specific genes (angiogenesis and metastasis)
hTR
some NF-κB target genes is decreased in the TERC knockout mice

22. conclusion

23. According to this study;
Do you have any idea for new research?