Caspase-mediated cleavage of the stacking protein GRASP65 is required for Golgi fragmentation during apoptosis.
AuthorsLane JD, Lucocq J, Pryde J, Barr FA, Woodman PG, Allan VJ, Lowe M
JournalJ Cell Biol
PubMed ID11815631
'The mammalian Golgi complex is comprised of a ribbon of stacked cisternal membranes often located in the pericentriolar region of the cell. Here, we report that during apoptosis the Golgi ribbon is fragmented into dispersed clusters of tubulo-vesicular membranes. We have found that fragmentation is caspase dependent and identified GRASP65 ... More
A novel role for microtubules in apoptotic chromatin dynamics and cellular fragmentation.
AuthorsMoss DK, Betin VM, Malesinski SD, Lane JD
JournalJ Cell Sci
PubMed ID16723742
'Dramatic changes in cellular dynamics characterise the apoptotic execution phase, culminating in fragmentation into membrane-bound apoptotic bodies. Previous evidence suggests that actin-myosin plays a dominant role in apoptotic cellular remodelling, whereas all other cytoskeletal elements dismantle. We have used fixed cells and live-cell imaging to confirm that interphase microtubules rapidly ... More
Distinct phosphoinositide 3-kinases mediate mast cell degranulation in response to G-protein-coupled versus FcepsilonRI receptors.
AuthorsWindmiller DA, Backer JM
JournalJ Biol Chem
PubMed ID12529321
'Phosphoinositide (PI) 3-kinases are critical regulators of mast cell degranulation. The Class IA PI 3-kinases p85/p110beta and p85/p110delta but not p85/p110alpha are required for antigen-mediated calcium flux in RBL-2H3 cells (Smith, A. J., Surviladze, Z., Gaudet, E. A., Backer, J. M., Mitchell, C. A., and Wilson, B. S. et al., ... More
Cholesterol-induced apoptotic macrophages elicit an inflammatory response in phagocytes, which is partially attenuated by the Mer receptor.
AuthorsLi Y, Gerbod-Giannone MC, Seitz H, Cui D, Thorp E, Tall AR, Matsushima GK, Tabas I
JournalJ Biol Chem
PubMed ID16380374
'Macrophage apoptosis and the ability of phagocytes to clear these apoptotic cells are important processes in advanced atherosclerosis. Phagocytic clearance not only disposes of dead cells but usually elicits an anti-inflammatory response. To study this process in a model of advanced lesional macrophage death, macrophages rendered apoptotic by free cholesterol ... More
CD45-mediated fodrin cleavage during galectin-1 T cell death promotes phagocytic clearance of dying cells.
AuthorsPang M, He J, Johnson P, Baum LG,
JournalJ Immunol
PubMed ID19454697
'Disassembly and phagocytic removal of dying cells is critical to maintain immune homeostasis. The factors that regulate fragmentation and uptake of dying lymphocytes are not well understood. Degradation of fodrin, a cytoskeletal linker molecule that attaches CD45 to the actin cytoskeleton, has been described in apoptotic cells, although no specific ... More
Control of type I interferon-induced cell death by Orai1-mediated calcium entry in T cells.
AuthorsYue C, Soboloff J, Gamero AM,
JournalJ Biol Chem
PubMed ID22144678
Store-operated Ca(2+) entry (SOCE) is an essential process in T cell activation. SOCE is controlled by the Ca(2+) release-activated Ca(2+) (CRAC) channel encoded by the gene Orai1 that is expressed on the plasma membrane and activated by STIM1 when ER Ca(2+) stores are depleted. Our earlier work showed that a ... More
Noninvasive imaging of cell death using an Hsp90 ligand.
AuthorsPark D, Don AS, Massamiri T, Karwa A, Warner B, MacDonald J, Hemenway C, Naik A, Kuan KT, Dilda PJ, Wong JW, Camphausen K, Chinen L, Dyszlewski M, Hogg PJ,
JournalJ Am Chem Soc
PubMed ID21322555
Cell death plays a central role in normal physiology and in disease. Common to apoptotic and necrotic cell death is the eventual loss of plasma membrane integrity. We have produced a small organoarsenical compound, 4-(N-(S-glutathionylacetyl)amino)phenylarsonous acid, that rapidly accumulates in the cytosol of dying cells coincident with loss of plasma ... More
Pivotal advance: macrophages become resistant to cholesterol-induced death after phagocytosis of apoptotic cells.
AuthorsCui D, Thorp E, Li Y, Wang N, Yvan-Charvet L, Tall AR, Tabas I,
JournalJ Leukoc Biol
PubMed ID17576822
One of the most important functions of macrophages is the phagocytosis of apoptotic cells (ACs). ACs deliver large amounts membrane-derived cholesterol to phagocytes, which, if not handled properly, can be cytotoxic. In atherosclerosis, where the ACs are cholesterol-loaded, this situation is exaggerated, because the ACs deliver both endogenous membrane cholesterol ... More
Accessibility of nuclear chromatin by DNA binding polyamides.
Pyrrole-imidazole polyamides bind DNA with affinities comparable to those of transcriptional regulatory proteins and inhibit the DNA binding activities of components of the transcription apparatus. If polyamides are to be useful for the regulation of gene expression in cell culture experiments, one pivotal issue is accessibility of specific sites in ... More
PUMA Dissociates Bax and Bcl-X(L) to induce apoptosis in colon cancer cells.
AuthorsMing L, Wang P, Bank A, Yu J, Zhang L
JournalJ Biol Chem
PubMed ID16608847
PUMA is a BH3-only Bcl-2 family protein that plays an essential role in DNA damage-induced apoptosis. PUMA interacts with anti-apoptotic Bcl-2 and Bcl-X(L) and is dependent on Bax to induce apoptosis. In this study, we investigated how the interactions of PUMA with the antiapoptotic proteins coordinate with Bax to initiate ... More
Low-Dose Radiation Conditioning Enables CAR T Cells to Mitigate Antigen Escape.
AuthorsDeSelm C, Palomba ML, Yahalom J, Hamieh M, Eyquem J, Rajasekhar VK, Sadelain M
JournalMol Ther
PubMed ID30415658
CD19 chimeric antigen receptors (CARs) have demonstrated great efficacy against a range of B cell malignancies. However, antigen escape and, more generally, heterogeneous antigen expression pose a challenge to applying CAR therapy to a wide range of cancers. We find that low-dose radiation sensitizes tumor cells to immune rejection by ... More
AuthorsMoutal A, Villa LS, Yeon SK, Householder KT, Park KD, Sirianni RW, Khanna R
JournalMol Neurobiol
PubMed ID28660485
Glioblastoma (GBM) is an aggressive primary brain tumor. The rapid growth and the privileged provenance of the tumor within the brain contribute to its aggressivity and poor therapeutic targeting. A poor prognostic factor in glioblastoma is the deletion or mutation of the Nf1 gene. This gene codes for the protein ... More
FTY720 induces non-canonical phosphatidylserine externalization and cell death in acute myeloid leukemia.
AuthorsYoung MM, Bui V, Chen C, Wang HG
JournalCell Death Dis
PubMed ID31699964
FTY720 (fingolimod) is a FDA-approved sphingosine analog that is phosphorylated in vivo to modulate sphingosine-1-phosphate receptor (S1PR) signaling for immunosuppression in patients with refractory multiple sclerosis. FTY720 also exhibits promising anticancer efficacy in several preclinical models. While FTY720-induced cytotoxicity is not due to S1PR signaling, the mechanism remains unclear and ... More
PIM protein kinases regulate the level of the long noncoding RNA H19 to control stem cell gene transcription and modulate tumor growth.
AuthorsSingh N, Padi SKR, Bearss JJ, Pandey R, Okumura K, Beltran H, Song JH, Kraft AS, Olive V
JournalMol Oncol
PubMed ID32146726
The proviral integration site for Moloney murine leukemia virus (PIM) serine/threonine kinases have an oncogenic and prosurvival role in hematological and solid cancers. However, the mechanism by which these kinases drive tumor growth has not been completely elucidated. To determine the genes controlled by these protein kinases, we carried out ... More