scholarly journals Disintegrin-Like Peptides Derived from Naturally-Occurring Proteins: A Proposed Adjunct Treatment for Cancer Therapy: A Commentary

Author(s):  
Mizejewski GJ

Disintegrins constitute a group of small proteins or peptides (45-85 amino acids) that function as natural antagonists of integrin receptor-dependent cell activities. The integrins themselves comprise a superfamily of hetero-dimeric (alpha and beta chains) transmembrane cell surface receptors whose functions include cell adhesion, growth, migration, and angiogenesis. In contrast, the disintegrins comprise groups of two types of molecules, namely, a) short proteins or peptides comprising insect and animal venoms; and b) intrinsic sub domain sequence fragments or short motifs present on large mammalian metalloprotease enzymes. Certain disintegrins bind specifically to tri-amino acid sequences (RGD, LGD etc) located on integrins beta-1 and beta-3 chains of the hetero complex receptors. Binding at such sites can inhibit or block cell migration, angiogenesis, metastasis, and platelet aggregation. Recently, small disintegrin-like peptides from naturally-occurring proteins have likewise been reported to inhibit growth and adhesion functions associated with integrin-dependent cell activities. The present report describes examples of such disintegrin-like peptides and provides support for their proposed use in adjunct cancer therapy.

Plant Disease ◽  
2010 ◽  
Vol 94 (2) ◽  
pp. 276-276 ◽  
Author(s):  
W. Menzel ◽  
S. Winter ◽  
K. R. Richert-Pöggeler

Hollyhocks are popular garden plants and selected cultivars of Alcea rosea (family Malvaceae) are widespread in Germany. In spring 2009, dozens of A. rosea plants displaying strong vein clearing and veinal yellowing symptoms were found in private gardens in Hannover, Lower Saxony. Electron microscopic examinations of negatively stained adsorption preparations of five randomly selected samples of symptomatic plants or their offshoots revealed flexuous filamentous particles resembling those of potyviruses. Sap extracts also reacted strongly positive in an antigen coated plate (ACP)-ELISA with the broad-spectrum potyvirus antiserum AS-0573/I (DSMZ, Braunschweig, Germany). RNA extracts (RNeasy Kit, Qiagen, Valencia, CA) of the above mentioned leaf samples were used as templates in reverse transcription (RT)-PCR assays with potyvirus specific primers (2) that have been shown to amplify the 3′ terminus of the genome of many potyvirus species. For extracts from symptomatic samples, this resulted in a consistent amplification of an ~1.6-kbp fragment, whereas no products were obtained from RNA extracts of asymptomatic plants. From one positive sample, the amplified fragment was cloned and one clone was partially sequenced. The nucleotide (nt) and amino acid sequences showed the highest identities (81 to 83% and 87 to 90%, respectively) to GenBank sequences FJ539084, FM212972, EU884405, and FJ561293 of the potyvirus Malva vein clearing virus (MVCM). On the basis of these identity values and according to the species demarcation criteria in the genus Potyvirus, the virus can be regarded as a German isolate of the recently sequenced MVCV (3,4). Direct sequencing of the 5′-end of the amplified RT-PCR fragment revealed sequences of only one potyvirus species. The virus isolate has been submitted to the DSMZ Plant Virus Collection (Braunschweig, Germany) under accession PV-0963 and the sequence obtained from the cloned cDNA is deposited in GenBank (GQ856544). In addition, sap from affected leaves was mechanically inoculated onto sets of herbaceous indicator plants (Chenopodium quinoa, C. foliosum, C. murale, C. amaranticolor, Datura stramonium, Nicotiana benthamiana, N. hesperis, Petunia hybrida, and Solanum lycopersicum) of which only C. quinoa plants became infected. Symptoms of weak chlorosis along and beside veins of inoculated leaves, but not systemic leaves, became visible 2 weeks postinoculation. Symptomatic leaves contained flexuous filamentous particles and ACP-ELISA and RT-PCR confirmed virus presence. The partially sequenced amplicon showed 99% nt identity to the sequence from the cloned cDNA. To our knowledge, this is the first report of a MVCV isolate naturally occurring in A. rosea and C. quinoa is the first host identified that does not belong to the plant family Malvaceae. In contrast, the MVCV isolate used in the host range study of Lunello et al. (4) did not infect A. rosea and C. quinoa, confirming previous host range descriptions by Brunt et al. (1). Since MVCV infections of hollyhocks seem to cause only leaf symptoms and do not noticeably affect growth or flowering of the plants, this will hopefully not impair the usability of this popular garden plant. References: (1) A. A. Brunt et al. Descriptions and Lists from the VIDE Database. Online publication. Version: 16th January, 1997. (2) J. Chen et al. Arch. Virol. 146:757, 2001. (3) A. Hein Phytopathol. Z. 28:205, 1957. (4) P. Lunello et al. Virus Res. 140:91, 2009.


Development ◽  
1993 ◽  
Vol 118 (3) ◽  
pp. 845-858 ◽  
Author(s):  
G.H. Yee ◽  
R.O. Hynes

The integrins are a family of cell surface receptors for extracellular matrix proteins and counter-receptors on other cells. We have used the polymerase chain reaction to identify a novel integrin receptor beta subunit in Drosophila melanogaster. The deduced amino acid sequence of this subunit, which we have termed beta v (beta-neu), indicates that it has several unusual properties. The beta v subunit is roughly 33% identical with each of the previously sequenced vertebrate and Drosophila beta subunits and is lacking four of the 56 cysteine residues characteristic of most members of this protein family. The expression of the beta v gene is strikingly restricted. It is temporally regulated, with maximal expression occurring at 12–15 hours of embryonic development. In situ hybridization analyses and antibody localization on whole-mount embryos reveal that beta v expression is tissue-specific and confined to the developing midgut endoderm and its precursors during embryogenesis. Tissue specificity of expression is maintained through later stages of development as beta v transcripts are found exclusively in the larval midgut. Within this structure, beta v transcripts are especially concentrated in the cells of the midgut imaginal islands which give rise to the adult midgut.


Blood ◽  
2003 ◽  
Vol 102 (1) ◽  
pp. 169-179 ◽  
Author(s):  
Cunji Gao ◽  
Weiyong Sun ◽  
Melpo Christofidou-Solomidou ◽  
Motoshi Sawada ◽  
Debra K. Newman ◽  
...  

Abstract Programmed cell death, or apoptosis, is a tightly regulated, naturally occurring process by which damaged or unwanted cells are removed. Dysregulated apoptosis has been implicated in a variety of pathophysiological conditions, including degenerative diseases, tissue remodeling, and tumorogenesis. The decision to live or die results from integration of numerous environmental signals transmitted by specific classes of cell surface receptors that bind hormones, growth factors, or components of the extracellular matrix. Here we show that platelet endothelial cell adhesion molecule-1 (PECAM-1), a homophilic-binding member of the immunoreceptor tyrosine-based inhibitory motif (ITIM) family of inhibitory receptors, functions prominently to inhibit apoptosis in naturally occurring vascular cells subjected to apoptotic stimuli. Murine endothelial cells and human T lymphocytes lacking PECAM-1 were found to be far more sensitive than their PECAM-1—expressing counterparts to multiple death signals that stimulate Bax, a multidomain, proapoptotic member of the Bcl-2 family that plays a central role in mitochondrial dysfunction-dependent apoptosis. In addition, PECAM-1 markedly suppressed Bax overexpression—induced cytochrome c release, caspase activation, and nuclear fragmentation. Amino acid substitutions within PECAM-1's extracellular homophilic binding domain, or within its cytoplasmic ITIM, completely abolished PECAM-1—mediated cytoprotection. Taken together, these data implicate PECAM-1 as a novel and potent suppressor of Bax-mediated apoptosis and suggest that members of the immunoglobulin gene (Ig) superfamily, like cell surface integrins, may also transmit survival signals into blood and vascular cells. (Blood. 2003;102:169-179)


Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 830
Author(s):  
Erum Shoeb ◽  
Uzma Badar ◽  
Srividhya Venkataraman ◽  
Kathleen Hefferon

Naturally occurring viral nanomaterials have gained popularity owing to their biocompatible and biodegradable nature. Plant virus nanoparticles (VNPs) can be used as nanocarriers for a number of biomedical applications. Plant VNPs are inexpensive to produce, safe to administer and efficacious as treatments. The following review describes how plant virus architecture facilitates the use of VNPs for imaging and a variety of therapeutic applications, with particular emphasis on cancer. Examples of plant viruses which have been engineered to carry drugs and diagnostic agents for specific types of cancer are provided. The drug delivery system in response to the internal conditions is known as stimuli response, recently becoming more applicable using plant viruses based VNPs. The review concludes with a perspective of the future of plant VNPs and plant virus-like particles (VLPs) in cancer research and therapy.


1993 ◽  
Vol 13 (6) ◽  
pp. 3384-3391 ◽  
Author(s):  
S W Hiebert

Studies of naturally occurring mutations of the RB1 tumor suppressor gene have indicated that the E1A/T antigen-binding domain is important for pRb function. Mutations engineered within the C-terminal 135 amino acids of pRb also abrogate its growth-suppressive function during the G1 interval of the cell cycle. Both the pRb E1A/T antigen-binding domain and the C-terminal domain are required for interaction with the E2F transcription factor. A series of mutated pRb proteins has been used to define the C-terminal sequences which determine E2F binding, adenovirus E2 promoter inhibition, and negative growth control. Deletion of the C terminus to residue 870 allowed full pRb function, while further deletion to residue 841 inactivated pRb in each assay. Amino acid sequences immediately C-terminal to the E1A/T antigen-binding domain were absolutely required for pRb activity. Mutations which prevented pRb from interacting with E2F also eliminated pRb-mediated E2 promoter repression and inactivated the ability of pRb to suppress cell growth.


1994 ◽  
Vol 14 (10) ◽  
pp. 6506-6514 ◽  
Author(s):  
D L Barber ◽  
A D D'Andrea

The erythropoietin (EPO) receptor and the interleukin-2 (IL-2) receptor beta-chain subunit are members of the cytokine receptor superfamily. They have conserved primary amino acid sequences in their cytoplasmic domains and activate phosphorylation of common substrates, suggesting common biochemical signaling mechanisms. We have generated a cell line, CTLL-EPO-R, that contains functional cell surface receptors for both EPO and IL-2. CTLL-EPO-R cells demonstrated similar growth kinetics in EPO and IL-2. Stimulation with EPO resulted in the rapid, dose-dependent tyrosine phosphorylation of JAK2. In contrast, stimulation with IL-2 or the related cytokine IL-4 resulted in the rapid, dose-dependent tyrosine phosphorylation of JAK1 and an additional 116-kDa protein. This 116-kDa protein was itself immunoreactive with a polyclonal antiserum raised against JAK2 and appears to be a novel member of the JAK kinase family. Immune complex kinase assays confirmed that IL-2 and IL-4 activated JAK1 and EPO activated JAK2. These results demonstrate that multiple biochemical pathways are capable of conferring a mitogenic signal in CTLL-EPO-R cells and that the EPO and IL-2 receptors interact with distinct JAK kinase family members within the same cellular background.


Biochemistry ◽  
1997 ◽  
Vol 36 (17) ◽  
pp. 5120-5127 ◽  
Author(s):  
John F. McDonald ◽  
Amit M. Shah ◽  
Ruth A. Schwalbe ◽  
Walter Kisiel ◽  
Björn Dahlbäck ◽  
...  

1998 ◽  
Vol 18 (2) ◽  
pp. 846-858 ◽  
Author(s):  
Issay Kitabayashi ◽  
Kohmei Ida ◽  
Fumiko Morohoshi ◽  
Akihiko Yokoyama ◽  
Naoko Mitsuhashi ◽  
...  

ABSTRACT The AML1-CBFβ transcription factor complex is essential for the definitive hematopoiesis of all lineages and is the most frequent target of chromosomal rearrangements in human leukemia. In the t(8;21) translocation associated with acute myeloid leukemia (AML), theAML1(CBFA2/PEBP2αB) gene is juxtaposed to theMTG8(ETO/CDR) gene. We show here that the resultant AML1-MTG8 gene product specifically and strongly interacts with an 85-kDa phosphoprotein. Molecular cloning of cDNA indicated that the AML1-MTG8-binding protein (MTGR1) is highly related to MTG8 and similar to Drosophila Nervy. Comparison of amino acid sequences among MTGR1, MTG8, and Nervy revealed four evolutionarily conserved regions (NHR1 to NHR4). Ectopic expression of AML1-MTG8 in L-G murine myeloid progenitor cells inhibits differentiation to mature neutrophils and induces cell proliferation in response to granulocyte colony-stimulating factor (G-CSF). Analysis with C-terminal deletion mutants of AML1-MTG8 indicated that the region of 51 residues (488 to 538), which contains NHR2, is essential for the induction of G-CSF-dependent cell proliferation. Immunoprecipitation analysis indicates that this region is required for AML1-MTG8 to form a stable complex with MTGR1. Overexpression of MTGR1 stimulates AML1-MTG8 to induce G-CSF-dependent proliferation of L-G cells and to interfere with AML1-dependent transcription. These results suggest that AML1-MTG8 could function as a complex with MTGR1 and that the complex might be important in promoting leukemogenesis.


Sign in / Sign up

Export Citation Format

Share Document