Biochemistry, Biophysics, and Structural Biology Commons^™

Vectorial Acylation In Saccharomyces Cerevisiae, Zhiying Zou, Fumin Tong, Nils J. Færgeman, Claus Børsting, Paul N. Black, Concetta Dirusso

Department of Biochemistry: Faculty Publications

In Saccharomyces cerevisiae Fat1p and fatty acyl-CoA synthetase (FACS) are hypothesized to couple import and activation of exogenous fatty acids by a process called vectorial acylation. Molecular genetic and biochemical studies were used to define further the functional and physical interactions between these proteins. Multicopy extragenic suppressors were selected in strains carrying deletions in FAA1 and FAA4 or FAA1 and FAT1. Each strain is unable to grow under synthetic lethal conditions when exogenous long-chain fatty acids are required, and neither strain accumulates the fluorescent long-chain fatty acid C₁-BODIPY-C₁₂ indicating a fatty acid transport defect. By using these …

Dictyostelium Lvsb Mutants Model The Lysosomal Defects Associated With Chediak-Higashi Syndrome, Ed Harris, Ning Wang, Wei-I Wu, Alisha Weatherford, Arturo De Lozanne, James Cardelli

Department of Biochemistry: Faculty Publications

Chediak-Higashi syndrome is a genetic disorder caused by mutations in a gene encoding a protein named LYST in humans (“lysosomal trafficking regulator”) or Beige in mice. A prominent feature of this disease is the accumulation of enlarged lysosome-related granules in a variety of cells. The genome of Dictyostelium discoideum contains six genes encoding proteins that are related to LYST/Beige in amino acid sequence, and disruption of one of these genes, lvsA (large volume sphere), results in profound defects in cytokinesis. To better understand the function of this family of proteins in membrane trafficking, we have analyzed mutants disrupted in lvsA, …

The Atp:Co(I)Rrinoid Adenosyltransferase (Coba) Enzyme Of Salmonella Enterica Requires The 2’-Oh Group Of Atp For Function And Yields Inorganic Triphosphate As Its Reaction Byproduct, Maris V. Fonseca, Nicole R. Baun, Alexander R. Horswill, Ivan Rayment, Jorge C. Escalante-Semerena

Department of Biochemistry: Faculty Publications

The specificity of the ATP:corrinoid adenosyltransferase

(CobA) enzyme of Salmonella enterica serovar

Typhimurium LT2 for its nucleotide substrate was

tested using ATP analogs and alternative nucleotide donors.

The enzyme showed broad specificity for the nucleotide

base and required the 2’-OH group of the ribosyl

moiety of ATP for activity. ³¹P NMR spectroscopy

was used to identify inorganic triphosphate (PPP_i) as

the byproduct of the reaction catalyzed by the CobA

enzyme. Cleavage of triphosphate into pyrophosphate

and orthophosphate did not occur, indicating that

triphosphate cleavage was not required for release of

the adenosylcorrinoid product. Triphosphate was …

Rabd, A Dictyostelium Rab14-Related Gtpase, Regulates Phagocytosis And Homotypic Phagosome And Lysosome Fusion, Ed Harris, James Cardelli

Department of Biochemistry: Faculty Publications

RabD, a Dictyostelium Rab14-related GTPase, localizes in the endo-lysosomal pathway and contractile vacuole system of membranes. Cell lines expressing dominant-negative RabD were defective in endocytosis, endosomal membrane flow and homotypic lysosome fusion. In support of a role for RabD in fusion, cells overexpressing constitutively active RabD^Q67L accumulated enlarged hydrolase-rich acidic vesicles ringed with GFP-RabD, consistent with RabD directly regulating lysosome fusion. To determine whether RabD also regulated phagocytosis and/or homotypic phagosome fusion (a process stimulated by many intracellular pathogens), cells overexpressing dominant-active (RabD^Q67L) or dominant-negative (Rab^N121I) RabD were analyzed microscopically and biochemically. The rate of …

Selenoprotein R Is A Zinc-Containing Stereo-Specific Methionine Sulfoxide Reductase, Gregory V. Kryukov, R. Abhilash Kumar, Ahmet Koc, Zhaohul Sun, Vadim N. Gladyshev

Department of Biochemistry: Faculty Publications

Selenoprotein R (SelR) is a mammalian selenocysteine-containing protein with no known function. Here we report that cysteine homologs of SelR are present in all organisms except certain parasites and hyperthermophiles, and this pattern of occurrence closely matches that of only one protein, peptide methionine sulfoxide reductase (MsrA). Moreover, in several genomes, SelR and MsrA genes are fused or clustered, and their expression patterns suggest a role of both proteins in protection against oxidative stress. Consistent with these computational screens, growth of Saccharomyces cerevisiae SelR and MsrA mutant strains was inhibited, and the strain lacking both genes could not grow, in …

Kinetic Properties Of Bifunctional 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase From Spinach Leaves, Jennifer E. Markham, Nicholas J. Kruger

Department of Biochemistry: Faculty Publications

A cDNA encoding 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase was isolated from a Spinacia oleracea leaf library and used to ex­press a recombinant enzyme in Escherichia coli and Spodoptera frugiperda cells. The insoluble protein expressed in E. coli was purified and used to raise antibodies. Western blot analysis of a protein extract from spinach leaf showed a single band of 90.8 kDa. Soluble protein was purified to homogeneity from S. frugiperda cells infected with recombinant baculovirus harboring the isolated cDNA. The soluble protein had a molecular mass of 320 kDa, estimated by gel filtration chromatography, and a subunit size of 90.8 kDa. The purified pro­tein …

Transitions In Histone Acetylation Reveal Boundaries Of Three Separately Regulated Neighboring Loci, Michael D. Litt, Melanie A. Simpson, Felix Recillas-Targa, Marie-Noelle Prioleau, Gary Felsenfeld

Department of Biochemistry: Faculty Publications

We have studied developmentally regulated patterns of histone acetylation at high resolution across ~54 kb of DNA containing three independently regulated but neighboring genetic loci. These include a folate receptor gene, a 16 kb condensed chromatin region, the chicken β-globin domain and an adjacent olfactory receptor gene. Within these regions the relative levels of acetylation appear to fall into three classes. The condensed chromatin region maintains the lowest acetylation at every developmental stage. Genes that are inactive show similarly low levels, but activation results in a dramatic increase in acetylation. The highest levels of acetylation are seen at regulatory sites …

Correlation Between Histone Lysine Methylation And Developmental Changes At The Chicken Β-Globin Locus, Michael D. Litt, Melanie A. Simpson, Miklos Gaszner, D. David Allis, Gary Felsenfeld

Department of Biochemistry: Faculty Publications

Methylation of histones at specific residues plays an important role in transcriptional regulation. Chromatin immunoprecipitation of dimethylated lysine 9 on histone H3 across 53 kilobases of the chicken β-globin locus during erythropoiesis shows an almost complete anticorrelation between regions of elevated lysine 9 methylation and acetylation. Lysine 9 is methylated most over constitutive condensed chromatin and developmentally inactive globin genes. In contrast, lysine 4 methylation of histone H3 correlates with H3 acetylation. These results lead us to propose a mechanism by which the insulator in the β-globin locus can protect the globin genes from being silenced by adjacent condensed chromatin.

Reversible Phosphorylation Of Photosynthetic Pep Carboxylase: Studies On C4-Leaf Pp2a And Recombinant Pepc-Kinase From Cam-Induced Mesembryanthemum Crystallinum, L. Dong, N. V. Ermolova, M. A. Cushman, T. Taybi, J. C. Cushman, Raymond Chollet

Department of Biochemistry: Faculty Publications

The activity and allosteric properties of plant PEPC are controlled posttranslationally by specific reversible phosphorylation of a strictly conserved Ser residue near the N-terminus. This up/down-modulation is catalyzed by a transcriptionally regulated, seemingly dedicated Ser/Thr kinase (PpcK) and an opposing Ser/Thr phosphatase (PP2A). We have now partially purified and characterized the native form of this largely “neglected” PP2A from maize leaves using various chromatographic and affinity matrices, and C₄ [³²P]PEPC as substrate (Dong et al., 2001, Planta [in press]). The results indicate that the C₄-leaf holoenzyme is analogous to yeast and mammalian PP2As in regards …

Unexpected Post-Translational Modifications And Novel Sequence-Structure Relationships Revealed By The Crystal Structure Of Chlamydomonas Reinhardtii Rubisco, T. C. Taylor, A. Backlund, R. J. Spreitzer, I. Andersson

Department of Biochemistry: Faculty Publications

The crystal structure of Rubisco from Chlamydomonas reinhardtii has been solved to 1.4 Å resolution. In addition to clear electron density for the carbamate on lys-201, the active site magnesium ion and the inhibitor 2-CABP, there was unexpected but unambiguous electron density for further specific post-translational modification. The N-terminus of the mature small subunit is methylated. The large subunit contains two methylcysteine residues (256 & 369) and two hydroxyproline residues (104 & 151). The small subunit from Chlamydomonas shows a structure more similar to that of the higher green plants than that from other algae of known structure. An extensive …

Can Negligible Levels Of Rubisco Activase, Be The Reason For Decreased Rubisco Activity Levels In Guard Cells?, S. Madhavan, P. Echtenkamp

Department of Biochemistry: Faculty Publications

Rubisco in guard cell chloroplasts has been a subject of controversy for decades. Several studies have unequivocally confirmed not only the presence of Rubisco in guard cells but also found it to be catalytically active. Based on a cell basis, the amount of Rubisco in guard cells is suggested to be in the range of 0.6 to 1.4 % whereas its activity is reported to be in the range of 0.35 to 0.5%, of a mesophyll cell. This low activity may be due a) to a low Rubisco content, and/or, b) to either the absence or an inactive functional activation …

Monoclonal Light Chain–Mesangial Cell Interactions: Early Signaling Events And Subsequent Pathologic Effects, William J. Russell, James Cardelli, Ed Harris, R. John Baier, Guillermo A. Herrera

Department of Biochemistry: Faculty Publications

Glomerulopathic monoclonal light chains (G-LC) interact with mesangial cells (MC), resulting in alterations of mesangial homeostasis. Early signaling events control mitogenic activities and cytokine production, which in turn participate in the subsequent pathologic events. Mesangial homeostasis is affected in two very different ways, depending on whether the G-LC is from a patient with light chain deposition disease (LCDD) or light chain–related amyloidosis (AL-Am). In contrast, tubulopathic (T)-LC chains from patients with myeloma cast nephropathy do not significantly interact with MC and result in no alterations in mesangial homeostasis. Therefore, understanding early events in the monoclonal LC–MC interactions is fundamental. MC …

The Wasp-Like Protein Scar Regulates Macropinocytosis, Phagocytosis And Endosomal Membrane Flow In Dictyostelium, David J. Seastone, Ed Harris, Lesly A. Temesvari, James E. Bear, Charles L. Saxe, James Cardelli

Department of Biochemistry: Faculty Publications

Scar, a member of the WASp protein family, was discovered in Dictyostelium discoideum during a genetic screen for second-site mutations that suppressed a developmental defect. Disruption of the scar gene reduced the levels of cellular F-actin by 50%. To investigate the role of Scar in endocytosis, phagocytosis and endocytic membrane trafficking, processes that depend on actin polymerization, we have analyzed a Dictyostelium cell line that is genetically null for Scar. Rates of fluid phase macropinocytosis and phagocytosis are significantly reduced in the scar^- cell-line. In addition, exocytosis of fluid phase is delayed in these cells and movement of fluid …

Rab11-Like Gtpase Associates With And Regulates The Structure And Function Of The Contractile Vacuole System In Dictyostelium, Ed Harris, Kunito Yoshida, James Cardelli, John Bush

Department of Biochemistry: Faculty Publications

Screening of a cDNA library revealed the existence of a Dictyostelium cDNA encoding a protein 80% identical at the amino acid level to mammalian Rab11. Subcellular fractionation and immunofluorescence studies revealed that DdRab11 was exclusively associated with the ATPase proton pump-rich contractile vacuole membrane system, consisting of a reticular network and bladder-like vacuoles. Video microscopy of cells expressing GFP-DdRab11 revealed that this Rab was associated with contractile vacuolar bladders undergoing formation, fusion and expulsion of water. The association of DdRab11 with contractile vacuole membranes was disrupted when cells were exposed to either hypo-osmotic conditions or an inhibitor of the ATPase …

Selenoprotein Oxidoreductase With Specificity For Thioredoxin And Glutathione Systems, Qi-An Sun, Leo Kirnarsky, Simon Sherman, Vadim N. Gladyshev

Department of Biochemistry: Faculty Publications

Thioredoxin (Trx) and glutathione (GSH) systems are considered to be two major redox systems in animal cells. They are reduced by NADPH via Trx reductase (TR) or oxidized GSH (GSSG) reductase and further supply electrons for deoxyribonucleotide synthesis, antioxidant defense, and redox regulation of signal transduction, transcription, cell growth, and apoptosis. We cloned and characterized a pyridine nucleotide disulfide oxidoreductase, Trx and GSSG reductase (TGR), that exhibits specificity for both redox systems. This enzyme contains a selenocysteine residue encoded by the TGA codon. TGR can reduce Trx, GSSG, and a GSH-linked disulfide in in vitro assays. This unusual substrate specificity …

The Cia5 Gene Controls Formation Of The Carbon Concentrating Mechanism In Chlamydomonas Reinhardtii, Youbin Xiang, Jun Zhang, Donald P. Weeks

Department of Biochemistry: Faculty Publications

Wild-type Chlamydomonas reinhardtii cells shifted from high concentrations (5%) of CO2 to low, ambient levels (0.03%) rapidly increase transcription of mRNAs from several CO₂-responsive genes. Simultaneously, they develop a functional carbon concentrating mechanism that allows the cells to greatly increase internal levels of CO₂ and HCO₃. The cia5 mutant is defective in all of these phenotypes. A newly isolated gene, designated Cia5, restores transformed cia5 cells to the phenotype of wild-type cells. The 6,481-bp gene produces a 5.1-kb mRNA that is present constitutively in light in high and low CO₂ both in …

Structural And Functional Conservation At The Boundaries Of The Chicken Β-Globin Domain, Noriko Saitoh, Adam C. Bell, Felix Recillas-Targa, Adam G. West, Melanie A. Simpson, Michael Pikaart, Gary Felsenfeld

Department of Biochemistry: Faculty Publications

We show that the 3' boundary of the chicken β -globin locus bears striking structural similarities to the 5' boundary. In erythroid cells a clear transition in DNase I sensitivity of chromatin at the 3' end of the locus is observed, the location of this transition is marked by a constitutive DNase I hypersensitive site (HS), and DNA spanning this site has the enhancer-blocking capacity of an insulator. This HS contains a binding site for the transcription factor CTCF. As in the case of the 5' insulator, the CTCF site is both necessary and sufficient for the enhancer-blocking activity of …

Insect Cellular Reactions To The Lipopolysaccharide Component Of The Bacterium Serratia Marcescens Are Mediated By Eicosanoids, Jon C. Bedick, R L. Pardy, R. W. Howard, David W. Stanley

Department of Biochemistry: Faculty Publications

Nodulation, which begins with the formation of cellular microaggregates, is the predominant cellular defense reaction to bacterial infections in insects. We suggested that these reactions to bacterial infections are mediated by eicosanoids. The lipopolysaccharide (LPS) component of some bacterial cells stimulates defense reactions in mammals and insects. Here, we report on experiments designed to test the hypothesis that eicosanoids mediate microaggregation reactions to LPS. Injections of LPS (purified from the bacterium, Serratia marcescens) into larvae of the tenebrionid beetle, Zophobas atratus, stimulated microaggregation reactions in a dose-dependent manner. Treatments with eicosanoid-biosynthesis inhibitors immediately prior to LPS challenge sharply …

Rbcs Suppressor Mutations Improve The Thermal Stability And Co2/O2 Specificity Of Rbcl-Mutant Ribulose-1,5-Bisphosphate Carboxylaseyoxygenase, Yu-Chan Du, Seokjoo Hong, Robert J. Spreitzer

Department of Biochemistry: Faculty Publications

In the green alga Chlamydomonas reinhardtii, a Leu²⁹⁰-to-Phe (L²⁹⁰F) substitution in the large subunit of ribulose-1,5-bisphosphate carboxylaseyoxygenase (Rubisco), which is coded by the chloroplast rbcL gene, was previously found to be suppressed by second-site Ala222-to-Thr and Val²⁶²-to-Leu substitutions. These substitutions complement the photosynthesis deficiency of the L290F mutant by restoring the decreased thermal stability, catalytic efficiency, and CO₂/O₂ specificity of the mutant enzyme back to wild-type values. Because residues 222, 262, and 290 interact with the loop between β strands A and B of the Rubisco small subunit, which is …

Multiple Factors Independently Regulate Hila And Invasion Gene Expression In Salmonella Enterica Serovar Typhimurium, Robin L. Lucas, C. Phoebe Lostroh, Concetta C. Dirusso, Michael P. Spector, Barry L. Wanner, Catherine A. Lee

Department of Biochemistry: Faculty Publications

HilA activates the expression of Salmonella enterica serovar Typhimurium invasion genes. To learn more

about regulation of hilA, we isolated Tn5 mutants exhibiting reduced hilA and/or invasion gene expression. In

addition to expected mutations, we identified Tn5 insertions in pstS, fadD, flhD, flhC, and fliA. Analysis of the

pstS mutant indicates that hilA and invasion genes are repressed by the response regulator PhoB in the absence

of the Pst high-affinity inorganic phosphate uptake system. This system is required for negative control of the

PhoR-PhoB two-component regulatory system, suggesting that hilA expression may …

Multiple Factors Independently Regulate Hila And Invasion Gene Expression In Salmonella Enterica Serovar Typhimurium, Robin L. Lucas, C. Phoebe Lostroh, Concetta C. Dirusso, Michael P. Spector, Barry L. Wanner, Catherine A. Lee

Department of Biochemistry: Faculty Publications

HilA activates the expression of Salmonella enterica serovar Typhimurium invasion genes. To learn more

about regulation of hilA, we isolated Tn5 mutants exhibiting reduced hilA and/or invasion gene expression. In

addition to expected mutations, we identified Tn5 insertions in pstS, fadD, flhD, flhC, and fliA. Analysis of the

pstS mutant indicates that hilA and invasion genes are repressed by the response regulator PhoB in the absence

of the Pst high-affinity inorganic phosphate uptake system. This system is required for negative control of the

PhoR-PhoB two-component regulatory system, suggesting that hilA expression may …

Two-Step Processing Of Human Frataxin By Mitochondrial Processing Peptidase, Patrizia Cavadini, Jiri Adamec, Franco Taroni, Oleksandr Gakh, Grazia Isaya

Department of Biochemistry: Faculty Publications

We showed previously that maturation of the human

frataxin precursor (p-fxn) involves two cleavages by the

mitochondrial processing peptidase (MPP). This observation

was not confirmed by another group, however,

who reported only one cleavage. Here, we demonstrate

conclusively that MPP cleaves p-fxn in two sequential

steps, yielding a 18,826-Da intermediate (i-fxn) and a

17,255-Da mature (m-fxn) form, the latter corresponding

to endogenous frataxin in human tissues. The two cleavages

occur between residues 41–42 and 55–56, and both

match the MPP consensus sequence RX ↓ (X/S). Recombinant

rat and yeast MPP catalyze the pài step 4 and 40 …

Biochemical And Biophysical Analysis Of The Intracellular Lipid Binding Proteins Of Adipocytes, Melanie A. Simpson, Vince J. Licata, Natalie Ribarik Coe, David A. Bernlohr

Department of Biochemistry: Faculty Publications

Adipocytes express two lipid-binding proteins; the major one termed the adipocyte lipid-binding protein or aP2 (ALBP/aP2) and a minor one referred to as the keratinocyte lipid-binding protein (KLBP). In order to evaluate the potential physiological roles for these proteins, their biochemical and biophysical properties have been analyzed and compared. ALBP/aP2 and KLBP exhibit similar binding affinities for most long-chain fatty acids; however, ALBP/aP2 exhibits a two to three-fold increased affi nity for myristic, palmitic, oleic and linoleic acids, the predominant fatty acids of adipocytes. As measured by guanidinium hydrochloride denaturation, the stability of ALBP/aP2 is nearly 3 kcal/mol greater than …

Melanoma Chondroitin Sulphate Proteoglycan Regulates Cell Spreading Through Cdc42, Ack-1 And P130Cas, Kathryn M. Eisenmann, James B. Mccarthy, Melanie A. Simpson, Patricia J. Keely, Jun-Lin Guan, Kouichi Tachibana, Louis Lim, Ed Manser, Leo T. Furcht, Joji Iida

Department of Biochemistry: Faculty Publications

Melanoma chondroitin sulphate proteoglycan (MCSP) is a cell-surface antigen that has been implicated in the growth and invasion of melanoma tumors. Although this antigen is expressed early in melanoma progression, its biological function is unknown. MCSP can stimulate the integrin-α4β1-mediated adhesion and spreading of melanoma cells. Here we show that stimulated MCSP recruits tyrosine- phosphorylated p130cas, an adaptor protein important in tumor cell motility and invasion. MCSP stimulation also results in a pronounced activation and recruitment of the Rho-family GTPase Cdc42. MCSP-induced spreading of melanoma cells is dependent upon active Cdc42, a Cdc42-associated tyrosine kinase (Ack-1) and tyrosine phosphorylation of …

An Insulator Element And Condensed Chromatin Region Separate The Chicken Β-Globin Locus From An Independently Regulated Erythroid-Specific Folate Receptor Gene, Marie-Noelle Prioleau, Pascale Nony, Melanie A. Simpson, Gary Felsenfeld

Department of Biochemistry: Faculty Publications

We have identified a folate receptor gene upstream of the chicken β-globin locus and separated from it by a 16 kbp region of silent chromatin. We find that this receptor is expressed only at a stage of erythroid differentiation (CFU-E) preceding the activation of β-globin genes, consistent with the role of folate receptors in proliferation. This discovery raises the question of how these two loci are regulated during erythropoiesis. Our data suggest that the folate receptor gene and the β-globin locus are regulated independently. We show that a 3.3 kbp DNA region upstream of the folate receptor gene is sufficient …

Posttranscriptional Regulation Of Mammalian Methionine Synthase By B12, Sumedha Gulati, Lawrence C. Brody, Ruma V. Banerjee

Department of Biochemistry: Faculty Publications

Methionine synthase is one of two key enzymes involved in the removal of the metabolite, homocysteine. Elevated homocysteine levels constitute a risk factor for cardiovascular diseases and for neural tube defects. In cell culture, the activity of methionine synthase is enhanced several-fold by supplementation with its cofactor, B₁₂. The mechanism of this regulation is unknown, although it has been ascribed to a shift from apoenzyme to holoenzyme. Using sensitive assay techniques as well as a combination of Northern and Western analyses, we demonstrate that the effect of B,, on induction of methionine synthase activity is paralleled by an …

Yeast And Human Frataxin Are Processed To Mature Form In Two Sequential Steps By The Mitochondrial Processing Peptidase, Steven S. Branda, Patrizia Cavadini, Jiri Adamec, Frantisek Kalousek, Franco Taroni, Grazia Isaya

Department of Biochemistry: Faculty Publications

Frataxin is a nuclear-encoded mitochondrial protein which is deficient in Friedreich’s ataxia, a hereditary neurodegenerative disease. Yeast mutants lacking the yeast frataxin homologue (Yfh1p) show iron accumulation in mitochondria and increased sensitivity to oxidative stress, suggesting that frataxin plays a critical role in mitochondrial iron homeostasis and free radical toxicity. Both Yfh1p and frataxin are synthesized as larger precursor molecules that, upon import into mitochondria, are subject to two proteolytic cleavages, yielding an intermediate and a mature size form. A recent study found that recombinant rat mitochondrial processing peptidase (MPP) cleaves the mouse frataxin precursor to the intermediate but not …

Early And Late Endosomal Compartments Of Entamoeba Histolytica Are Enriched In Cysteine Proteases, Acid Phosphatase And Several Ras-Related Rab Gtpases, Lesly A. Temesvari, Ed Harris, Samuel L. Stanley Jr., James Cardelli

Department of Biochemistry: Faculty Publications

Pure populations of early and late endosomes of Entamoeba histolytica were isolated by magnetic fractionation and characterized. It was shown that these vesicles were enriched in acid phosphatase and cysteine protease activities. An important virulence factor, a 27-kDa cysteine protease, was also enriched in early and late endosomes of E. histolytica. These data suggest that E. histolytica hydrolases reside in compartments that are part of or communicate with the endosomal pathway. To begin to identify the role of Rab GTPases in E. histolytica, an oligonucleotide approach was employed to screen an E. histolytica cDNA library for genes encoding …

Telomerase Expression In Chickens: Constitutive Activity In Somatic Tissues And Down-Regulation In Culture, Ranga N. Venkatesan, Carolyn Price

Department of Biochemistry: Faculty Publications

Although human and rodent telomeres have been studied extensively, very little is known about telomere dynamics in other vertebrates. Moreover, our current dependence on mice as a model for human tumorigenesis and aging poses a problem because human and mouse telomere biology is very different. To explore whether chickens might provide a more useful model, we have examined telomerase activity and telomere length in chicken tissues as well as in primary cell cultures. Although chicken telomeres resemble human telomeres in that they are 8–20 kb in length, the distribution of telomerase activity in chickens resembles what is found in mice. …

Intracellular Lipid-Binding Proteins And Their Genes, David A. Bernlohr, Melanie A. Simpson, Ann Vogel Hertzel, Leonard J. Banaszak

Department of Biochemistry: Faculty Publications

Intracellular lipid-binding proteins are a family of low-molecularweight single-chain polypeptides that form 1:1 complexes with fatty acids, retinoids, or other hydrophobic ligands. These proteins are products of a large multigene family of unlinked loci distributed throughout the genome. Each lipid-binding protein exhibits a distinctive pattern of tissue distribution. Transcriptional control, regulated by a combination of peroxisome proliferator activated receptors and CCAAT/enhancer-binding proteins, allows for a variety of both cell and tissue-specific expression patterns. In some cells, fatty acids increase the expression of the lipid-binding protein genes. Fatty acids, or their metabolites, are activators of the peroxisome proliferator–activated receptor family of …