One of the deepest branches in the tree of life separates the Archaea from the Bacteria. These prokaryotic groups have distinct cellular systems including fundamentally different phospholipid membrane Show more
One of the deepest branches in the tree of life separates the Archaea from the Bacteria. These prokaryotic groups have distinct cellular systems including fundamentally different phospholipid membrane bilayers. This dichotomy has been termed the lipid divide and possibly bestows different biophysical and biochemical characteristics on each cell type. Classic experiments suggest that bacterial membranes (formed from lipids extracted from Escherichia coli, for example) show permeability to key metabolites comparable to archaeal Show less
Author Manuscript The gasotransmitter hydrogen sulfide (H2S) is thought to be involved in the post-translational modification of cysteine residues to produce reactive persulfides. A persulfide-specifi Show more
Author Manuscript The gasotransmitter hydrogen sulfide (H2S) is thought to be involved in the post-translational modification of cysteine residues to produce reactive persulfides. A persulfide-specific chemoselective proteomics approach with mammalian cells has identified a broad range of zinc finger (ZF) proteins as targets of persulfidation. Parallel studies with isolated ZFs show that persulfidation is mediated by zinc(II), O2, and H2S, and intermediates involving oxygen- and sulfur-based radicals were detected by mass spectrometry and optical spectroscopies. A small Show less
The treatment of colorectal cancer (CRC) with FOLFOX shows some efficacy, but
these tumors quickly develop resistance to this treatment. We have observed
increased phosphorylation of AKT1/mTOR/4EBP1 a Show more
The treatment of colorectal cancer (CRC) with FOLFOX shows some efficacy, but
these tumors quickly develop resistance to this treatment. We have observed
increased phosphorylation of AKT1/mTOR/4EBP1 and levels of p21 in
FOLFOX-resistant CRC cells. We have identified a small molecule, NSC49L, that
stimulates protein phosphatase 2A (PP2A) activity, downregulates the AKT1/
mTOR/4EBP1-axis, and inhibits p21 translation. We have provided evidence
that NSC49L- and TRAIL-mediated sensitization is synergistically induced in
p21-knockdown CRC cells, which is reversed in p21-overexpressing cells. p21
binds with procaspase 3 and prevents the activation of caspase 3. We have shown
that TRAIL induces apoptosis through the activation of caspase 3 by NSC49Lmediated downregulation of p21 translation, and thereby cleavage of procaspase 3 into caspase 3. NSC49L does not affect global protein synthesis. These
studies provide a mechanistic understanding of NSC49L as a PP2A agonist, and
how its combination with TRAIL sensitizes FOLFOX-resistant CRC cells. Show less