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Articles 1 - 8 of 8
Full-Text Articles in Medicine and Health Sciences
Essential Role Of The Crk Family-Dosage In Digeorge-Like Anomaly And Metabolic Homeostasis, Akira Imamoto, Sewon Ki, Leiming Li, Kazunari Iwamoto, Venkat Maruthamuthu, John Devany, Ocean Lu, Suxiang Zhang, Takuji Yamada, Akiyoshi Hirayama, Shinji Fukuda, Yutaka Suzuki, Mariko Okada
Essential Role Of The Crk Family-Dosage In Digeorge-Like Anomaly And Metabolic Homeostasis, Akira Imamoto, Sewon Ki, Leiming Li, Kazunari Iwamoto, Venkat Maruthamuthu, John Devany, Ocean Lu, Suxiang Zhang, Takuji Yamada, Akiyoshi Hirayama, Shinji Fukuda, Yutaka Suzuki, Mariko Okada
Mechanical & Aerospace Engineering Faculty Publications
CRK and CRKL (CRK-like) encode adapter proteins with similar biochemical properties. Here, we show that a 50% reduction of the family-combined dosage generates developmental defects, including aspects of DiGeorge/del22q11 syndrome in mice. Like the mouse homologs of two 22q11.21 genes CRKL and TBX1, Crk and Tbx1 also genetically interact, thus suggesting that pathways shared by the three genes participate in organogenesis affected in the syndrome. We also show that Crk and Crkl are required during mesoderm development, and Crk/Crkl deficiency results in small cell size and abnormal mesenchyme behavior in primary embryonic fibroblasts. Our systems-wide analyses reveal impaired …
Functional Importance Of Lipin Phosphorylation, Stephanie Elizabeth Hood
Functional Importance Of Lipin Phosphorylation, Stephanie Elizabeth Hood
Graduate Theses and Dissertations
Highly conserved throughout evolution, lipins are dual functioning proteins found from yeast to humans. Functioning in the cytoplasm as phosphatidate phosphatase enzymes (PAP), lipins produce diacylglycerol that serves as a precursor for neutral fats and membrane phospholipids. Alternatively, nuclear lipins are responsible for the regulation of metabolic genes. Interestingly, both the mammalian lipin 1 paralog and the single Drosophila Lipin ortholog are highly phosphorylated proteins. Target of rapamycin (TOR) has previously been identified as one of the kinases that controls the subcellular localization of both lipin 1 and Drosophila Lipin. However, other serine and threonine kinases are predicted to be …
Regulation Of Lipogenesis By Cyclin-Dependent Kinase 8-Mediated Control Of Srebp-1., Xiaoping Zhao, Daorong Feng, Qun Wang, Arian Abdulla, Xiao-Jun Xie, Jie Zhou, Yan Sun, Ellen S Yang, Lu-Ping Liu, Bhavapriya Vaitheesvaran, Lauren Bridges, Irwin J Kurland, Randy Strich, Jian-Quan Ni, Chenguang Wang, Johan Ericsson, Jeffrey E Pessin, Jun-Yuan Ji, Fajun Yang
Regulation Of Lipogenesis By Cyclin-Dependent Kinase 8-Mediated Control Of Srebp-1., Xiaoping Zhao, Daorong Feng, Qun Wang, Arian Abdulla, Xiao-Jun Xie, Jie Zhou, Yan Sun, Ellen S Yang, Lu-Ping Liu, Bhavapriya Vaitheesvaran, Lauren Bridges, Irwin J Kurland, Randy Strich, Jian-Quan Ni, Chenguang Wang, Johan Ericsson, Jeffrey E Pessin, Jun-Yuan Ji, Fajun Yang
Department of Cancer Biology Faculty Papers
Altered lipid metabolism underlies several major human diseases, including obesity and type 2 diabetes. However, lipid metabolism pathophysiology remains poorly understood at the molecular level. Insulin is the primary stimulator of hepatic lipogenesis through activation of the SREBP-1c transcription factor. Here we identified cyclin-dependent kinase 8 (CDK8) and its regulatory partner cyclin C (CycC) as negative regulators of the lipogenic pathway in Drosophila, mammalian hepatocytes, and mouse liver. The inhibitory effect of CDK8 and CycC on de novo lipogenesis was mediated through CDK8 phosphorylation of nuclear SREBP-1c at a conserved threonine residue. Phosphorylation by CDK8 enhanced SREBP-1c ubiquitination and protein …
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 …
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 …
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 …
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 …
Epigenetics And The Estrogen Receptor, Jennifer E. Leader, Chenuang Wang, Vladimir M. Popov, Maofu Fu, Richard G. Pestell
Epigenetics And The Estrogen Receptor, Jennifer E. Leader, Chenuang Wang, Vladimir M. Popov, Maofu Fu, Richard G. Pestell
Department of Cancer Biology Faculty Papers
The position effect variegation in Drosophila and Schizosaccharomyces pombe, and higher-order chromatin structure regulation in yeast, is orchestrated by modifier genes of the Su(var) group, (e.g., histone deacetylases ([HDACs]), protein phosphatases) and enhancer E(Var) group (e.g., ATP [adenosine 5'-triphosphate]-dependent nucleosome remodeling proteins). Higher-order chromatin structure is regulated in part by covalent modification of the N-terminal histone tails of chromatin, and histone tails in turn serve as platforms for recruitment of signaling modules that include nonhistone proteins such as heterochromatin protein (HP1) and NuRD. Because the enzymes governing chromatin structure through covalent modifications of histones (acetylation, methylation, phosphorylation, ubiquitination) can also …