RT Journal Article
SR Electronic
T1 CDK1 dependent phosphorylation of hTERT contributes to cancer progression
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 556514
DO 10.1101/556514
A1 Mami Yasukawa
A1 Yoshinari Ando
A1 Taro Yamashita
A1 Yoko Matsuda
A1 Shisako Shoji
A1 Masaki S. Morioka
A1 Hideya Kawaji
A1 Kumiko Shiozawa
A1 Takaya Abe
A1 Shinji Yamada
A1 Mika K. Kaneko
A1 Yukinari Kato
A1 Yasuhide Furuta
A1 Tadashi Kondo
A1 Mikako Shirouzu
A1 Yoshihide Hayashizaki
A1 Shuichi Kaneko
A1 Kenkichi Masutomi
YR 2019
UL http://biorxiv.org/content/early/2019/02/21/556514.abstract
AB The telomerase reverse transcriptase is upregulated in the majority of human cancers and contributes directly to cell transformation. Here we report that hTERT is phosphorylated at threonine 249 during mitosis by the serine/threonine kinase CDK1. Clinicopathological analyses revealed that phosphorylation of hTERT at threonine 249 occurs more frequently in advanced cancers. Using CRISPR/Cas9 genome editing, we introduced substitution mutations at threonine 249 in the endogenous hTERT locus and found that phosphorylation of threonine 249 is necessary for hTERT-mediated RNA dependent RNA polymerase (RdRP) activity but dispensable for reverse transcriptase activity. Cap Analysis of Gene Expression (CAGE) demonstrated that hTERT phosphorylation at 249 regulates the expression of specific genes that are necessary for cancer cell proliferation and tumor formation. These observations indicate that phosphorylation at threonine 249 regulates hTERT RdRP and contributes to cancer progression in a telomerase independent manner.