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AKIP1, PKA, and AIF: Human Embryonic Stem Cells Dance Towards Death
Author(s) -
King Charles C.,
Sastri Mira,
Pennypacker Juniper,
Taylor Susan S.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a987-a
Subject(s) - microbiology and biotechnology , embryonic stem cell , protein kinase a , biology , protein kinase b , endoderm , stem cell , signal transduction , progenitor cell , mapk/erk pathway , kinase , biochemistry , gene
One approach to treat type 1 diabetes is to coax human embryonic stem cells (hESCs) into endoderm and subsequently into glucose responsive, insulin producing beta cells. A recent report found that Sox17 and the cell surface receptor CXCR4 were upregulated as hESC formed definitive endoderm, and this transition was accompanied by massive apoptosis. In hematopoietic cells, CXCR4 signaling activates both anti‐apoptotic pathways (Akt and Erk) and pro‐apoptotic pathways (protein kinase A; PKA). In these studies, we will present data on the biochemical mechanism of survival and apoptosis of definitive endoderm. Specifically, we will describe the role a novel protein AKIP (A‐Kinase Interacting Protein) plays in this process. In cells, AKIP binds both the catalytic subunit of PKA and AIF (Apoptosis Inducing Factor); and we hypothesize that nuclear localization of AKIP is critical to initiate PKA‐mediated apoptosis. Recent studies have shown upon neddylation, AKIP represses NFkb transcription and may contribute to the suppression of pro‐survival genes seen in definitive endoderm. Thus, understanding the mechanisms by which CXCR4 signaling alters urvival and death of newly differentiated endodermal cells through AKIP, PKA, and AIF will provide fundamental information about signaling through this cytokine receptor and may significantly increase the number of endocrine and pancreatic progenitor cells during hESC differentiation.