Role of p53 and transcription-independent p53-induced apoptosis in shear-stimulated megakaryocytic maturation, particle generation, and platelet biogenesis.

ABSTRACT: Megakaryocytes (Mks) derive from hematopoietic stem and progenitor cells (HSPCs) in the bone marrow and develop into large, polyploid cells that eventually give rise to platelets. As Mks mature, they migrate from the bone marrow niche into the vasculature, where they are exposed to shear forces from blood flow, releasing Mk particles (platelet-like particles (PLPs), pro/preplatelets (PPTs), and Mk microparticles (MkMPs)) into circulation. We have previously shown that transcription factor p53 is important in Mk maturation, and that physiological levels of shear promote Mk particle generation and platelet biogenesis. Here we examine the role of p53 in the Mk shear-stress response. We show that p53 is acetylated in response to shear in both immature and mature Mks, and that decreased express

SUBMITTER: Luff SA 

PROVIDER: S-EPMC6145578 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature