Elucidating Proteoform Dynamics Underlying the Senescence Associated Secretory Phenotype.

ABSTRACT: Primary diploid cells exit the cell cycle in response to exogenous stress or oncogene activation through a process known as cellular senescence. This cell-autonomous tumor-suppressive mechanism is also a major mechanism operative in organismal aging. To date, temporal aspects of senescence remain understudied. Therefore, we use quantitative proteomics to investigate changes following forced HRAS^G12V expression and induction of senescence across 1 week in normal diploid fibroblasts. We demonstrate that global intracellular proteomic changes correlate with the emergence of the senescence-associated secretory phenotype and the switch to robust cell cycle exit. The senescence secretome reinforces cell cycle exit, yet is largely detrimental to tissue homeostasis. Previous studies of

SUBMITTER: Doubleday PF 

PROVIDER: S-EPMC7032038 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature