Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the gene encoding the low density lipoprotein receptor (LDLR). More than 50% of these mutations lead to receptor proteins that are completely or partly retained in the endoplasmic reticulum (ER). The mechanisms involved in the intracellular processing and ... More
BID-D59A is a potent inducer of apoptosis in primary embryonic fibroblasts.
AuthorsSarig R, Zaltsman Y, Marcellus RC, Flavell R, Mak TW, Gross A,
JournalJ Biol Chem
PubMed ID12519725
The proapoptotic activity of BID seems to solely depend upon its cleavage to truncated tBID. Here we demonstrate that expression of a caspase-8 non-cleavable (nc) BID-D59A mutant or expression of wild type (wt) BID induces apoptosis in Bid -/-, caspase-8 -/-, and wt primary MEFs. Western blot analysis indicated that ... More
Cell Cycle Regulation and p53 Activation by Protein Phosphatase 2Calpha.
AuthorsOfek P, Ben-Meir D, Kariv-Inbal Z, Oren M, Lavi S,
JournalJ Biol Chem
PubMed ID12514180
Protein phosphatase 2C (PP2C) dephosphorylates a broad range of substrates, regulating stress response and growth-related pathways in both prokaryotes and eukaryotes. We now demonstrate that PP2Calpha, a major mammalian isoform, inhibits cell growth and activates the p53 pathway. In 293 cell clones, in which PP2Calpha expression is regulated by a ... More
The gamma -secretase-cleaved C-terminal fragment of amyloid precursor protein mediates signaling to the nucleus.
Authors Gao Y; Pimplikar S W;
JournalProc Natl Acad Sci U S A
PubMed ID11742091
Sequential processing of the amyloid precursor protein (APP) by beta- and gamma-secretases generates the Abeta peptide, a major constituent of the senile plaques observed in Alzheimer's disease. The cleavage by gamma-secretase also results in the cytoplasmic release of a 59- or 57-residue-long C-terminal fragment (Cgamma). This processing resembles regulated intramembrane ... More
ATR is not required for p53 activation but synergizes with p53 in the replication checkpoint.
Authors Nghiem Paul; Park Peter K; Kim Ys Yong-son; Desai Bimal N; Schreiber Stuart L;
JournalJ Biol Chem
PubMed ID11711532
ATR (ataxia telangiectasia and Rad-3-related) is a protein kinase required for survival after DNA damage. A critical role for ATR has been hypothesized to be the regulation of p53 and other cell cycle checkpoints. ATR has been shown to phosphorylate p53 at Ser(15), and this damage-induced phosphorylation is diminished by ... More