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. Author manuscript; available in PMC: 2017 Feb 1.
Published in final edited form as: Arterioscler Thromb Vasc Biol. 2016 Feb;36(2):213–216. doi: 10.1161/ATVBAHA.115.306895

Figure 1. Regulated Intramembrane Proteolysis (RIP) of LRP1 regulates inflammation and endothelial cell proliferation.

Figure 1

a) RIP is a sequential process that first involves shedding of the LRP1 ectodomain, likely via a ADAM-like protease. This is followed by presenillin-1 mediated cleavge of shed LRP1 releasing the LRP1-ICD which can diffuse to the nucleus. b) In macrophages, the LRP1-ICD attenuates LPS-mediated inflammation by associating with IRF3 resulting in nuclear export of this transcription factor. c) In endothelial cells, the LRP1-ICD associates with PARP-1, attenuating its function. Under conditions of hypoxia, the interaction between LRP1-ICD and PARP-1 is weakened, and PARP-1 is freed to mediate the activation of Cdk2 and inhibition of Rb leading to angiogenesis.