The key role of the NAD biosynthetic enzyme nicotinamide mononucleotide adenylyltransferase in regulating cell functions

The photoreceptor cytoskeleton visualized

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100122800 ◽

1992 ◽

Vol 50 (1) ◽

pp. 480-481

Author(s):

Beth Burnside

Keyword(s):

Outer Segment ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Cell Polarization ◽

Synaptic Proteins ◽

Cell Functions ◽

Vertebrate Photoreceptor ◽

Numerous Cell ◽

Turn Over

The vertebrate photoreceptor provides a drammatic example of cell polarization. Specialized to carry out phototransduction at its distal end and to synapse with retinal interneurons at its proximal end, this long slender cell has a uniquely polarized morphology which is reflected in a similarly polarized cytoskeleton. Membranes bearing photopigment are localized in the outer segment, a modified sensory cilium. Sodium pumps which maintain the dark current critical to photosensory transduction are anchored along the inner segment plasma membrane between the outer segment and the nucleus.Proximal to the nucleus is a slender axon terminating in specialized invaginating synapses with other neurons of the retina. Though photoreceptor diameter is only 3-8u, its length from the tip of the outer segment to the synapse may be as great as 200μ. This peculiar linear cell morphology poses special logistical problems and has evoked interesting solutions for numerous cell functions. For example, the outer segment membranes turn over by means of a unique mechanism in which new disks are continuously added at the proximal base of the outer segment, while effete disks are discarded at the tip and phagocytosed by the retinal pigment epithelium. Outer segment proteins are synthesized in the Golgi near the nucleus and must be transported north through the inner segment to their sites of assembly into the outer segment, while synaptic proteins must be transported south through the axon to the synapse.The role of the cytoskeleton in photoreceptor motile processes is being intensely investigated in several laboratories.

Download Full-text

GSK-3α Inhibition in Drug-Resistant CML Cells Promotes Susceptibility to NK Cell-Mediated Lysis in an NKG2D- and NKp30-Dependent Manner

Cancers ◽

10.3390/cancers13081802 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1802

Author(s):

Nayoung Kim ◽

Mi Yeon Kim ◽

Woo Seon Choi ◽

Eunbi Yi ◽

Hyo Jung Lee ◽

...

Keyword(s):

Nk Cells ◽

Nk Cell ◽

Negative Regulator ◽

Target Cells ◽

Dependent Manner ◽

Cell Functions ◽

Cell Based Therapy ◽

Activating Receptors ◽

Gsk 3Β

Natural killer (NK) cells are innate cytotoxic lymphocytes that provide early protection against cancer. NK cell cytotoxicity against cancer cells is triggered by multiple activating receptors that recognize specific ligands expressed on target cells. We previously demonstrated that glycogen synthase kinase (GSK)-3β, but not GSK-3α, is a negative regulator of NK cell functions via diverse activating receptors, including NKG2D and NKp30. However, the role of GSK-3 isoforms in the regulation of specific ligands on target cells is poorly understood, which remains a challenge limiting GSK-3 targeting for NK cell-based therapy. Here, we demonstrate that GSK-3α rather than GSK-3β is the primary isoform restraining the expression of NKG2D ligands, particularly ULBP2/5/6, on tumor cells, thereby regulating their susceptibility to NK cells. GSK-3α also regulated the expression of the NKp30 ligand B7-H6, but not the DNAM-1 ligands PVR or nectin-2. This regulation occurred independently of BCR-ABL1 mutation that confers tyrosine kinase inhibitor (TKI) resistance. Mechanistically, an increase in PI3K/Akt signaling in concert with c-Myc was required for ligand upregulation in response to GSK-3α inhibition. Importantly, GSK-3α inhibition improved cancer surveillance by human NK cells in vivo. Collectively, our results highlight the distinct role of GSK-3 isoforms in the regulation of NK cell reactivity against target cells and suggest that GSK-3α modulation could be used to enhance tumor cell susceptibility to NK cells in an NKG2D- and NKp30-dependent manner.

Download Full-text

An autoantibody directed against human thrombin anion-binding exosite in a patient with arterial thrombosis: effects on platelets, endothelial cells, and protein C activation

Blood ◽

10.1182/blood.v84.6.1843.1843 ◽

1994 ◽

Vol 84 (6) ◽

pp. 1843-1850 ◽

Cited By ~ 14

Author(s):

E Arnaud ◽

M Lafay ◽

P Gaussem ◽

V Picard ◽

M Jandrot-Perrus ◽

...

Keyword(s):

Endothelial Cells ◽

Endothelial Cell ◽

Arterial Thrombosis ◽

Protein C ◽

Receptor Activation ◽

Anion Binding ◽

Thrombin Receptor ◽

Cell Functions ◽

Human Thrombin

Abstract An autoantibody, developed by a patient with severe and recurrent arterial thrombosis, was characterized to be directed against the anion- binding exosite of thrombin, and inhibited all thrombin interactions requiring this secondary binding site without interfering with the catalytic site. The effect of the antibody was studied on thrombin interactions with platelets and endothelial cells from human umbilical veins (HUVEC). The autoantibody specifically and concentration- dependently inhibited alpha-thrombin-induced platelet activation and prostacyclin (PGI2) synthesis from HUVEC. It had no effect when gamma- thrombin or the thrombin receptor activation peptide SFLLR were the inducers. The effect of the antibody on protein C activation has been studied. The antibody blocked the thrombin-thrombomodulin activation of protein C. The inhibition of the activation was maximal with a low concentration of thrombomodulin. The fact that the autoantibody inhibited concentration-dependent alpha-thrombin-induced platelet and endothelial cell functions emphasizes the crucial role of the anion- binding exosite of thrombin to activate its receptor. In regard to the pathology, the antibody inhibited two vascular processes implicated in thrombin-antithrombotic functions, PGI2 secretion, and protein C activation, which could be implicated in this arterial thrombotic disease.

Download Full-text

Nicotinamide mononucleotide adenylyltransferase, a nonhistone chromatin protein

Archives of Biochemistry and Biophysics ◽

10.1016/0003-9861(77)90005-4 ◽

1977 ◽

Vol 180 (1) ◽

pp. 34-40 ◽

Cited By ~ 5

Author(s):

Walter Cantarow ◽

B.David Stollar

Keyword(s):

Chromatin Protein ◽

Nicotinamide Mononucleotide ◽

Nicotinamide Mononucleotide Adenylyltransferase

Download Full-text

The Role of Proopiomelanocortin-Derived Peptides in Skin Fibroblast and Mast Cell Functions

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.1999.tb08684.x ◽

2006 ◽

Vol 885 (1) ◽

pp. 268-276 ◽

Cited By ~ 22

Author(s):

PATRIZIA TEOFOLI ◽

ALESSANDRA FREZZOLINI ◽

PIETRO PUDDU ◽

ORNELLA PITÀ ◽

ALAIN MAUVIEL ◽

...

Keyword(s):

Mast Cell ◽

Skin Fibroblast ◽

Cell Functions

Download Full-text

Functional role of miRNA-34A in smooth muscle cell functions and neointima formation

Atherosclerosis ◽

10.1016/j.atherosclerosis.2015.10.060 ◽

2016 ◽

Vol 244 ◽

pp. e3-e4 ◽

Cited By ~ 1

Author(s):

F. Yang ◽

Q. Chen ◽

G. Wen ◽

C. Zhang ◽

L.A. Luong ◽

...

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cell ◽

Muscle Cell ◽

Functional Role ◽

Neointima Formation ◽

Cell Functions

Download Full-text

Nicotinamide mononucleotide adenylyltransferase. Molecular and enzymic properties of the homogeneous enzyme from bakers' yeast

Biochemistry ◽

10.1021/bi00360a037 ◽

1986 ◽

Vol 25 (12) ◽

pp. 3725-3729 ◽

Cited By ~ 36

Author(s):

Paolo Natalini ◽

Silverio Ruggieri ◽

Nadia Raffaelli ◽

Giulio Magni

Keyword(s):

Nicotinamide Mononucleotide ◽

Nicotinamide Mononucleotide Adenylyltransferase

Download Full-text

The role of ferroptosis in breast cancer patients: a comprehensive analysis

Cell Death Discovery ◽

10.1038/s41420-021-00473-5 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Zeng-Hong Wu ◽

Yun Tang ◽

Hong Yu ◽

Hua-Dong Li

Keyword(s):

Breast Cancer ◽

T Cell ◽

Signaling Pathway ◽

Differentially Expressed Genes ◽

Function Analysis ◽

Cancer Prognosis ◽

Differentially Expressed ◽

Immune Checkpoints ◽

Cell Functions

AbstractBreast cancer (BC) affects the breast tissue and is the second most common cause of mortalities among women. Ferroptosis is an iron-dependent cell death mode that is characterized by intracellular accumulation of reactive oxygen species (ROS). We constructed a prognostic multigene signature based on ferroptosis-associated differentially expressed genes (DEGs). Moreover, we comprehensively analyzed the role of ferroptosis-associated miRNAs, lncRNAs, and immune responses. A total of 259 ferroptosis-related genes were extracted. KEGG function analysis of these genes revealed that they were mainly enriched in the HIF-1 signaling pathway, NOD-like receptor signaling pathway, central carbon metabolism in cancer, and PPAR signaling pathway. Fifteen differentially expressed genes (ALOX15, ALOX15B, ANO6, BRD4, CISD1, DRD5, FLT3, G6PD, IFNG, NGB, NOS2, PROM2, SLC1A4, SLC38A1, and TP63) were selected as independent prognostic factors for BC patients. Moreover, T cell functions, including the CCR score, immune checkpoint, cytolytic activity, HLA, inflammation promotion, para-inflammation, T cell co-stimulation, T cell co-inhibition, and type II INF responses were significantly different between the low-risk and high-risk groups of the TCGA cohort. Immune checkpoints between the two groups revealed that the expressions of PDCD-1 (PD-1), CTLA4, LAG3, TNFSF4/14, TNFRSF4/8/9/14/18/25, and IDO1/2 among others were significantly different. A total of 1185 ferroptosis-related lncRNAs and 219 ferroptosis-related miRNAs were also included in this study. From the online database, we identified novel ferroptosis-related biomarkers for breast cancer prognosis. The findings of this study provide new insights into the development of new reliable and accurate cancer treatment options.

Download Full-text