biostudies-literatureDel Giudice RNINDS NIH HHSNCI NIH HHSe1097https://www.ebi.ac.uk/biostudies/studies/S-EPMC3973227biostudies-literatureUnknown5Amyloidogenic 'gain-of-function' mutations in apolipoprotein A-I (ApoA-I) gene (APOA1) result in systemic amyloidosis characterized by aggregate deposition and eventually cell death. However, how amyloidogenic variants of ApoA-I induce cell death is unknown. Here we report that one of the mechanisms by which amyloidogenic ApoA-I induces cell death is through attenuating anti-stress activity of angiogenin (ANG), a homeostatic protein having both pro-growth and pro-survival functions. Under growth conditions, ANG is located in nucleolus where it promotes ribosomal RNA (rRNA) transcription thereby stimulating cell growth. In adverse conditions, ANG is relocated to cytoplasm to promote damage repairs and cell survival. We find that in cells overexpressing the L75P-APOA1 mutant ANG expression iCell death & diseaseAmyloidogenic variant of apolipoprotein A-I elicits cellular stress by attenuating the protective activity of angiogenin.PMC3973227R01 CA105241R01 NS065237Del Giudice RPiccoli RSarcinelli CArciello AMonti DMHu GFfalseAmyloidogenic variant of apolipoprotein A-I elicits cellular stress by attenuating the protective activity of angiogenin.Amyloidogenic 'gain-of-function' mutations in apolipoprotein A-I (ApoA-I) gene (APOA1) result in systemic amyloidosis characterized by aggregate deposition and eventually cell death. However, how amyloidogenic variants of ApoA-I induce cell death is unknown. Here we report that one of the mechanisms by which amyloidogenic ApoA-I induces cell death is through attenuating anti-stress activity of angiogenin (ANG), a homeostatic protein having both pro-growth and pro-survival functions. Under growth conditions, ANG is located in nucleolus where it promotes ribosomal RNA (rRNA) transcription thereby stimulating cell growth. In adverse conditions, ANG is relocated to cytoplasm to promote damage repairs and cell survival. We find that in cells overexpressing the L75P-APOA1 mutant ANG expression i2014-01-01T00:00:00Z2014 Mar2025-04-20T02:48:24.575Z2019-03-27T01:24:19ZS-EPMC39732272460332510.1038/cddis.2014.45