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- Department of Cancer Biology Faculty Papers (4)
- Department of Molecular Physiology and Biophysics Faculty Papers (2)
- Department of Pathology, Anatomy, and Cell Biology Faculty Papers (2)
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Articles 1 - 12 of 12
Full-Text Articles in Medicine and Health Sciences
Micro Rna 145 Targets The Insulin Receptor Substrate-1 And Inhibits The Growth Of Colon Cancer Cells, Bin Shi, Laura Sepp-Lorenzino, Marco Prisco, Peter Linsley, Tiziana Deangelis, Renato Baserga
Micro Rna 145 Targets The Insulin Receptor Substrate-1 And Inhibits The Growth Of Colon Cancer Cells, Bin Shi, Laura Sepp-Lorenzino, Marco Prisco, Peter Linsley, Tiziana Deangelis, Renato Baserga
Department of Cancer Biology Faculty Papers
The insulin receptor substrate-1 (IRS-1), a docking protein for both the type 1 insulin-like growth factor receptor (IGF-IR) and the insulin receptor, is known to send a mitogenic, anti-apoptotic, and anti-differentiation signal. Several micro RNAs (miRs) are suggested by the data base as possible candidates for targeting IRS-1. We show here that one of the miRs predicted by the data base, miR145, whether transfected as a synthetic oligonucleotide or expressed from a plasmid, causes down-regulation of IRS-1 in human colon cancer cells. IRS-1 mRNA is not decreased by miR145, while it is down-regulated by an siRNA targeting IRS-1. Targeting of …
Microvascular Endothelial Cells Express A Phosphatidylserine Receptor: A Functionally Active Receptor For Phosphatidylserine-Positive Erythrocytes, Yamaja Setty, Suhita Gayen Betal
Microvascular Endothelial Cells Express A Phosphatidylserine Receptor: A Functionally Active Receptor For Phosphatidylserine-Positive Erythrocytes, Yamaja Setty, Suhita Gayen Betal
Department of Pediatrics Faculty Papers
Phosphatidylserine (PS)-positive erythrocytes adhere to endothelium and subendothelial matrix components. While thrombospondin mediates these inter-actions, it is unknown whether PS-associated erythrocyte-endothelial adhesion occurs in the absence of plasma ligands. Using ionophore-treated PS-expressing control HbAA erythrocytes, we demonstrate that PS-positive erythrocytes adhered to human lung microendothelial cells in the absence of plasma ligands, that this adhesion was enhanced following endothelial activation with IL-1alpha, TNF-alpha, LPS, hypoxia, and heme, and that this adhesive interaction was selective to erythrocyte PS. We next explored whether microendothelial cells express an adhesion receptor that recognizes cell surface-expressed PS (PSR) similar to that expressed on activated macrophages. …
Phosphorylation-Induced Conformational Switching Of Cpi-17 Produces A Potent Myosin Phosphatase Inhibitor, Masumi Eto, Toshio Kitazawa, Fumiko Matsuzawa, Sei-Ichi Aikawa, Jason A. Kirkbride, Noriyoshi Isozumi, Yumi Nishimura, David L. Brautigan, Shin-Ya Ohki
Phosphorylation-Induced Conformational Switching Of Cpi-17 Produces A Potent Myosin Phosphatase Inhibitor, Masumi Eto, Toshio Kitazawa, Fumiko Matsuzawa, Sei-Ichi Aikawa, Jason A. Kirkbride, Noriyoshi Isozumi, Yumi Nishimura, David L. Brautigan, Shin-Ya Ohki
Department of Molecular Physiology and Biophysics Faculty Papers
Phosphorylation of endogenous inhibitor proteins specific for type-1 Ser/Thr phosphatase (PP1) provides a mechanism for reciprocal coordination of kinase and phosphatase activities. Phosphorylation of Thr38 in the inhibitor protein CPI-17 transduces G-protein-mediated signaling into a > 1000-fold increase of inhibitory potency toward myosin phosphatase. We show here the solution NMR structure of phospho-T38-CPI-17 with r. m. s. d. of 0.36 ± 0.06 Å for the backbone secondary structure, which reveals how phosphorylation triggers a conformational change and exposes the PP1 inhibitory surface. This active conformation is stabilized by the formation of a hydrophobic core of intercalated side-chains, which is not formed …
Stabilization Of Smar1 Mrna By Pga2 Involves A Stem Loop Structure In The 5' Utr, Lakshminarasimhan Pavritha, Shravanti Rampalli, Surajit Sinha, Kadreppa Sreenath, Richard G. Pestell, Samit Chattopadhyay
Stabilization Of Smar1 Mrna By Pga2 Involves A Stem Loop Structure In The 5' Utr, Lakshminarasimhan Pavritha, Shravanti Rampalli, Surajit Sinha, Kadreppa Sreenath, Richard G. Pestell, Samit Chattopadhyay
Department of Cancer Biology Faculty Papers
Prostaglandins are anticancer agents known to inhibit tumor cell proliferation both in vitro and in vivo by affecting the mRNA stability. Here we report that a MAR-binding protein SMAR1 is a target of Prostaglandin A2 (PGA2) induced growth arrest. We identify a regulatory mechanism leading to stabilization of SMAR1 transcript. Our results show that a minor stem and loop structure present in the 5' UTR of SMAR1 (1-UTR) is critical for nucleoprotein complex formation that leads to SMAR1 stabilization in response to PGA2. This results in an increased SMAR1 transcript and altered protein levels, that in turn causes downregulation of …
Gangliocytic Paraganglioma: Case Report And Review Of The Literature, Agnes Witkiewicz, Avi Galler, Charles Yeo
Gangliocytic Paraganglioma: Case Report And Review Of The Literature, Agnes Witkiewicz, Avi Galler, Charles Yeo
Department of Surgery Faculty Papers
Gangliocytic paraganglioma is a rare tumor, which occurs nearly exclusively in the second portion of the duodenum. Generally, this tumor has a benign clinical course, although rarely, it may recur or metastasize to regional lymph nodes. Only one case with distant metastasis has been reported. We present a case of duodenal gangliocytic paraganglioma treated first by local resection followed by pylorus-preserving pancreaticoduodenectomy. Examination of the first specimen revealed focal nuclear pleomorphism and mitotic activity, in addition to the presence of three characteristic histologic components: epithelioid, ganglion, and spindle cell. In the subsequent pancreaticoduodenectomy specimen, there was no residual tumor identified …
Bladder Inflammatory Transcriptome In Response To Tachykinins: Neurokinin 1 Receptor-Dependent Genes And Transcription Regulatory Elements, Ricardo Saban, Cindy Simpson, Rajanikanth Vadigepalli, Sylvie Memet, Igor Dozmorov, Marcia R. Saban
Bladder Inflammatory Transcriptome In Response To Tachykinins: Neurokinin 1 Receptor-Dependent Genes And Transcription Regulatory Elements, Ricardo Saban, Cindy Simpson, Rajanikanth Vadigepalli, Sylvie Memet, Igor Dozmorov, Marcia R. Saban
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Background Tachykinins (TK), such as substance P, and their neurokinin receptors which are ubiquitously expressed in the human urinary tract, represent an endogenous system regulating bladder inflammatory, immune responses, and visceral hypersensitivity. Increasing evidence correlates alterations in the TK system with urinary tract diseases such as neurogenic bladders, outflow obstruction, idiopathic detrusor instability, and interstitial cystitis. However, despite promising effects in animal models, there seems to be no published clinical study showing that NK-receptor antagonists are an effective treatment of pain in general or urinary tract disorders, such as detrusor overactivity. In order to search for therapeutic targets that could …
Expression Of The Autoimmune Fcgr2b Nzw Allele Fails To Be Upregulated In Germinal Center B Cells And Is Associated With Increased Igg Production, S.M. Ziaur Rahman, H. Niu, D. Perry, Timothy L. Manser, L. Morel
Expression Of The Autoimmune Fcgr2b Nzw Allele Fails To Be Upregulated In Germinal Center B Cells And Is Associated With Increased Igg Production, S.M. Ziaur Rahman, H. Niu, D. Perry, Timothy L. Manser, L. Morel
Department of Microbiology and Immunology Faculty Papers
The inhibitory receptor FcγRIIb regulates B-cell functions. Genetic studies have associated Fcgr2b polymorphisms and lupus susceptibility in both humans and murine models, in which B cells express reduced FcγRIIb levels. Furthermore, FcγRIIb absence results in lupus on the appropriate genetic background, and lentiviral-mediated FcγRIIb overexpression prevents disease in the NZM2410 lupus mouse. The NZM2410/NZW allele Fcgr2b is, however, located in-between Sle1a and Sle1b, two potent susceptibility loci, making it difficult to evaluate Fcr2bNZW independent contribution. By using two congenic strains that each carries only Sle1a (B6.Sle1a(15–353)), or Fcr2bNZW in the absence of Sle1a or Sle1b (B6.Sle1(111–148)), we show that the …
Cell Fate Determination Factor Dach1 Inhibits C-Jun-Induced Contact-Independent Growth, Kongming Wu, Manran Liu, Anping Li, Howard Donninger, Mahadev Rao, Xuanmao Jiao, Michael P. Lisanti, Ales Cvekl, Michael Birrer, Richard G. Pestell
Cell Fate Determination Factor Dach1 Inhibits C-Jun-Induced Contact-Independent Growth, Kongming Wu, Manran Liu, Anping Li, Howard Donninger, Mahadev Rao, Xuanmao Jiao, Michael P. Lisanti, Ales Cvekl, Michael Birrer, Richard G. Pestell
Department of Cancer Biology Faculty Papers
The cell fate determination factor DACH1 plays a key role in cellular differentiation in metazoans. DACH1 is engaged in multiple context-dependent complexes that activate or repress transcription. DACH1 can be recruited to DNA via the Six1/Eya bipartite transcription (DNA binding/coactivator) complex. c-Jun is a critical component of the activator protein (AP)-1 transcription factor complex and can promote contact-independent growth. Herein, DACH1 inhibited c-Jun-induced DNA synthesis and cellular proliferation. Excision of c-Jun with Cre recombinase, in c-jun(f1/f1) 3T3 cells, abrogated DACH1-mediated inhibition of DNA synthesis. c-Jun expression rescued DACH1-mediated inhibition of cellular proliferation. DACH1 inhibited induction of c-Jun by physiological stimuli …
Association Of The Tensin N-Terminal Protein-Tyrosine Phosphatase Domain With The Alpha Isoform Of Protein Phosphatase-1 In Focal Adhesions, Masumi Eto, Jason Kirkbride, Elizabeth Elliott, Su Hao Lo, David L. Brautigan
Association Of The Tensin N-Terminal Protein-Tyrosine Phosphatase Domain With The Alpha Isoform Of Protein Phosphatase-1 In Focal Adhesions, Masumi Eto, Jason Kirkbride, Elizabeth Elliott, Su Hao Lo, David L. Brautigan
Department of Molecular Physiology and Biophysics Faculty Papers
Focal adhesions attach cultured cells to the extracellular matrix, and we found endogenous protein phosphatase-1alpha isoform (PP1alpha) localized in adhesions across the entire area of adherent fibroblasts. However, in fibroblasts migrating into a scrape wound or spreading after replating PP1alpha did not appear in adhesions near the leading edge but was recruited into other adhesions coincident in time and space with incorporation of tensin. Endogenous tensin and PP1alpha co-precipitated from cell lysates with isoform-specific PP1 antibodies. Chemical cross-linking of focal adhesion preparations with Lomant's reagent demonstrated molecular proximity of endogenous PP1alpha and tensin, whereas neither focal adhesion kinase nor vinculin …
Untangling The Signalling Wires, Boris N. Kholodenko Phd, Dsci
Untangling The Signalling Wires, Boris N. Kholodenko Phd, Dsci
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Mitogen-activated protein kinase (MAPK) cascades process myriads of stimuli, generating receptor-specific cellular outcomes. New work exploits emergent mathematics of network inference to reveal distinct feedback designs of the RAF/MEK/ERK cascade induced by two different growth factors. It shows that response specificity can arise from differential signal-induced wiring of overlapping protein networks.
Somatic Excision Demonstrates That C-Jun Induces Cellular Migration And Invasion Through Induction Of Stem Cell Factor, Sanjay Katiyar, Xuanmao Jiao, Erwin Wagner, Michael P. Lisanti, Richard G. Pestell
Somatic Excision Demonstrates That C-Jun Induces Cellular Migration And Invasion Through Induction Of Stem Cell Factor, Sanjay Katiyar, Xuanmao Jiao, Erwin Wagner, Michael P. Lisanti, Richard G. Pestell
Department of Cancer Biology Faculty Papers
Cancer cells arise through sequential acquisition of mutations in tumor suppressors and oncogenes. c-Jun, a critical component of the AP-1 complex, is frequently overexpressed in diverse tumor types and has been implicated in promoting cellular proliferation, migration, and angiogenesis. Functional analysis of candidate genetic targets using germ line deletion in murine models can be compromised through compensatory mechanisms. As germ line deletion of c-jun induces embryonic lethality, somatic deletion of the c-jun gene was conducted using floxed c-jun (c-junf/f) conditional knockout mice. c-jun-deleted cells showed increased cellular adhesion, stress fiber formation, and reduced cellular migration. The reduced migratory …
Inhibition Of Antiassociation Activity Of Translation Initiation Factor 3 By Paromomycin, Go Hirokawa, Hideko Kaji, Akira Kaji
Inhibition Of Antiassociation Activity Of Translation Initiation Factor 3 By Paromomycin, Go Hirokawa, Hideko Kaji, Akira Kaji
Department of Biochemistry and Molecular Biology Faculty Papers
The effect of paromomycin on the interaction of ribosomal subunits was studied. Paromomycin inhibited the antiassociation activity of initiation factor 3 (IF3). Furthermore, ribosomal subunits were associated to form 70S ribosomes by paromomycin even in the presence of 1 mM Mg(2+). Paromomycin did not inhibit the binding of IF3 to the 30S ribosomal subunits. On the other hand, IF3 bound to the 30S subunits was expelled by paromomycin-induced subunit association (70S formation). These results indicate that the stabilization of 70S ribosomes by paromomycin may in part be responsible for its inhibitory effects on translocation and ribosome recycling.