The cellular senescence of leukemia-initiating cells from acute lymphoblastic leukemia is postponed by β-Arrestin1 binding with P300-Sp1 to regulate hTERT transcription.

ABSTRACT: Although we previously reported that the self-renewal of leukemia-initiating cells of B-lineage acute lymphoblastic leukemia (B-ALL LICs) was regulated by β-Arrestin1, a multiple-function protein, the cellular senescence is critical for LICs fate and leukemia progress, and worthy for further investigation. Here we found that depletion of β-Arrestin1 extended the population doubling time and the percentage of senile cells, the signatures of cellular senescence, of B-ALL LICs. Moreover, lack of β-Arrestin1 enhanced the expression of proteins (CBX, HIRA) and genes (P53, P16) related to senescence in leukemic Reh cells and B-ALL-LICs-derived leukemic mice. Further results showed that loss of β-Arrestin1 induced senescence of Reh cells through mediating hTERT-telomerase-telomere axis, which was

SUBMITTER: Liu S 

PROVIDER: S-EPMC5603829 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature