Diverse regulatory manners of human telomerase reverse transcriptase

Table 3 The PTMs of hTERT

Enzyme	Site	Effects on hTERT/telomerase	Human cell model	Ref.
PTMs: Phosphorylation
AKT	Ser 824	telomerase activity ↑	melanoma cells	[149]
AKT	Ser 227	hTERT nuclear translocation ↑ cell immortalization ↑	lung carcinoma cells and foreskin fibroblast cells	[150]
AKT	Ser 227	hTERT binding with importin-α ↑ hTERT nuclear import ↑ telomerase activity ↑	breast cancer cells	[151]
PKCα, β, δ, ε, ζ	Unclear	hTERT association with HSP90 ↑ telomerase holoprotein integrity ↑ telomerase activation ↑ chemosensitivity to cisplatin ↓	head and neck cancer cells	[152]
PKCα	Unclear	telomerase activity ↑	breast cancer cells	[153]
SRC	Tyr 707	cytoplasm translocation ↑ antiapoptotic function ↑	embryonic kidney cells	[154]
SRC	Tyr 707	mitochondrial hTERT ↓	umbilical and vein endothelial cells	[155]
c-ABL	Tyr	telomerase activity ↓	embryonic kidney cells and breast cancer cells	[157]
Unclear	Unclear	nuclear translocation ↑	CD4⁺ T cells	[158]
PTMs: Dephosphorylation
SHP-2	Tyr 707	SRC kinase function↓ H2O2-induced hTERT nuclear export ↓nuclear telomerase activity ↑	endothelial cells	[156]
PTMs: Ubiquitination
MKRN1	Unclear	hTERT degradation ↑ telomerase activity ↓ telomere length ↓	lung carcinoma cells	[161]
HDM2	N-Lys 78, 94, 236, 339, 348	hTERT degradation ↑ protection against apoptosis ↓	colon cancer, lung carcinoma, osteosarcoma and embryonic kidney cells	[162]
CHIP	Unclear	hTERT associating with p23 ↓ hTERT nuclear translocation ↓ hTERT degradation ↑	lung carcinoma cells	[163]

ISSN: 1478-811X