Time‐series transcriptomics and proteomics reveal alternative modes to decode p53 oscillations

Molecular Systems Biology

Petra Balbi¹  Ashwini Jambhekar¹  Galit Lahav¹  Dan Lu¹  Marian Kalocsay¹  Alba Jiménez¹  Matthew J Berberich² 

[1] Department of Systems Biology Blavatnik Institute at Harvard Medical School Boston MA USA;Laboratory of Systems Pharmacology Blavatnik Institute at Harvard Medical School Boston MA USA;

关键词: decoding mechanisms;    network motifs;    p53 dynamics;    proteomics;    transcriptomics;   

DOI  :  10.15252/msb.202110588

来源: DOAJ

【 摘 要 】

Abstract The cell stress‐responsive transcription factor p53 influences the expression of its target genes and subsequent cellular responses based in part on its dynamics (changes in level over time). The mechanisms decoding p53 dynamics into subsequent target mRNA and protein dynamics remain unclear. We systematically quantified p53 target mRNA and protein expression over time under two p53 dynamical regimes, oscillatory and rising, using RNA‐sequencing and TMT mass spectrometry. Oscillatory dynamics allowed for a greater variety of dynamical patterns for both mRNAs and proteins. Mathematical modeling of empirical data revealed three distinct mechanisms that decode p53 dynamics. Specific combinations of these mechanisms at the transcriptional and post‐transcriptional levels enabled exclusive induction of proteins under particular dynamics. In addition, rising induction of p53 led to higher induction of proteins regardless of their functional class, including proteins promoting arrest of proliferation, the primary cellular outcome under rising p53. Our results highlight the diverse mechanisms cells employ to distinguish complex transcription factor dynamics to regulate gene expression.

【 授权许可】

Unknown