The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4

Cellular senescence is a terminal stress-activated program controlled by the p53 and p16(INK4a) tumor suppressor proteins. A striking feature of senescence is the senescence-associated secretory phenotype (SASP), a pro-inflammatory response linked to tumor promotion and aging. We have identified the transcription factor GATA4 as a senescence and SASP regulator. GATA4 is stabilized in cells undergoing senescence and is required for the SASP. Normally, GATA4 is degraded by p62-mediated selective autophagy, but this regulation is suppressed during senescence, thereby stabilizing GATA4. GATA4 in turn activates the transcription factor NF-κB to initiate the SASP and facilitate senescence. GATA4 activation depends…

• HH
  Howard Hughes Medical Institute
• AC
  American Cancer Society
• DR
  Damon Runyon Cancer Research Foundation
• GF
  Glenn Foundation for Medical Research
• AC
  American-Italian Cancer Foundation
• NI
  National Institutes of Health

  Awards: DP1OD006849, AG009909, AG017242, GM44664, AG046174