XBP1-KLF9 axis acts as a molecular rheostat to control the transition from adaptive to cytotoxic unfolded protein response

Elevation of ER stress above a critical threshold causes accumulation of XBP1s protein sufficient for binding to the promoter and activation of a gene encoding a transcription factor KLF9. In turn, KLF9 induces expression of two regulators of ER calcium storage, TRIM38B and ITRP1, facilitating additional calcium release from ER, exacerbation of ER stress, and cell death. Overall design: RNA was isolated from WI38 cells transduced with empty vector, KLF9 cDNA-expressing vector, control shRNA or 2 independent shRNAs to KLF9. RNA samples were subjected to deep sequencing using Illumina instrumentation.