'Deoxynucleoside triphosphates (dNTPs) used for mitochondrial DNA replication are mainly formed by phosphorylation of deoxynucleosides imported into mitochondria from the cytosol. We earlier obtained evidence for a mitochondrial 5''-nucleotidase (dNT2) with a pronounced specificity for dUMP and dTMP and suggested that the enzyme protects mitochondrial DNA replication from excess dTTP. ... More
Multiple lysine mutations in the C-terminal domain of p53 interfere with MDM2-dependent protein degradation and ubiquitination
AuthorsNakamura S, Roth JA, Mukhopadhyay T
JournalMol Cell Biol
PubMed ID11094089
'To investigate the effect of mutations in the p53 C-terminal domain on MDM2-mediated degradation, we introduced single and multiple point mutations into a human p53 cDNA at four putative acetylation sites (amino acid residues 372, 373, 381, and 382). Substitution of all four lysine residues by alanines (the A4 mutant) ... More
Ca2+/calmodulin-dependent protein kinase II is required for microcystin-induced apoptosis.
'The potent natural toxins microcystin, nodularin, and okadaic acid act rapidly to induce apoptotic cell death. Here we show that the apoptosis correlates with protein phosphorylation events and can be blocked by protein kinase inhibitors directed against the multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). The inhibitors used comprised a battery ... More
Molecular basis of the specific subcellular localization of the C2-like domain of 5-lipoxygenase.
Authors Kulkarni Shilpa; Das Sudipto; Funk Colin D; Murray Diana; Cho Wonhwa;
JournalJ Biol Chem
PubMed ID11796736
The activation of 5-lipoxygenase (5-LO) involves its calcium-dependent translocation to the nuclear envelope, where it catalyzes the two-step transformation of arachidonic acid into leukotriene A(4), leading to the synthesis of various leukotrienes. To understand the mechanism by which 5-LO is specifically targeted to the nuclear envelope, we studied the membrane ... More
New Human Breast Cancer Cells to Study Progesterone Receptor Isoform Ratio Effects and Ligand-independent Gene Regulation.
Authors Jacobsen Britta M; Richer Jennifer K; Schittone Stephanie A; Horwitz Kathryn B;
JournalJ Biol Chem
PubMed ID12021276
All known progesterone target cells coexpress two functionally different progesterone receptor (PR) isoforms: 120-kDa B-receptors (PR-B) and N-terminally truncated, 94-kDa A-receptors (PR-A). Their ratio varies in normal and malignant tissues. In human breast cancer cells, homodimers of progesterone-occupied PR-A or PR-B regulate different gene subsets. To study PR homo- and ... More
Inducible expression of a constitutively active mutant of mitogen-activated protein kinase kinase 7 specifically activates c-JUN NH2-terminal protein kinase, alters expression of at least nine genes, and inhibits cell proliferation.
Authors Wolter Sabine; Mushinski J Frederic; Saboori Ali M; Resch Klaus; Kracht Michael;
JournalJ Biol Chem
PubMed ID11714698
MKK7 is a recently discovered mitogen-activated protein kinase (MAPK) kinase that is unique in that it specifically activates only the c-JUN NH(2)-terminal protein kinase (JNK) family of enzymes. Very little is known about the biological role of MKK7. We generated inducible cell lines from the human embryonal kidney carcinoma cell ... More
Membrane targeting of C2 domains of phospholipase C-delta isoforms.
Authors Ananthanarayanan Bharath; Das Sudipto; Rhee Sue Goo; Murray Diana; Cho Wonhwa;
JournalJ Biol Chem
PubMed ID11706040
The C2 domain is a Ca(2+)-dependent membrane-targeting module found in many cellular proteins involved in signal transduction or membrane trafficking. To understand the mechanisms by which the C2 domain mediates the membrane targeting of PLC-delta isoforms, we measured the in vitro membrane binding of the C2 domains of PLC-delta1, -delta3, ... More