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Kristin Ann Anderson

Assistant Research Professor of Pharmacology & Cancer Biology
Pharmacology & Cancer Biology
DUMC Box 104775, 300 N Duke Street, Room 50-206, Durham, NC 27701
300 N Duke Street, 50-206, Durham, NC 27701

Selected Publications


Statin therapy inhibits fatty acid synthase via dynamic protein modifications.

Journal Article Nat Commun · May 10, 2022 Statins are a class of drug widely prescribed for the prevention of cardiovascular disease, with pleiotropic cellular effects. Statins inhibit HMG-CoA reductase (HMGCR), which converts the metabolite HMG-CoA into mevalonate. Recent discoveries have shown H ... Full text Link to item Cite

Deglutarylation of glutaryl-CoA dehydrogenase by deacylating enzyme SIRT5 promotes lysine oxidation in mice.

Journal Article J Biol Chem · April 2022 A wide range of protein acyl modifications has been identified on enzymes across various metabolic processes; however, the impact of these modifications remains poorly understood. Protein glutarylation is a recently identified modification that can be none ... Full text Link to item Cite

β-Cell-specific ablation of sirtuin 4 does not affect nutrient-stimulated insulin secretion in mice.

Journal Article Am J Physiol Endocrinol Metab · October 1, 2020 Sirtuins are a family of proteins that regulate biological processes such as cellular stress and aging by removing posttranslational modifications (PTMs). We recently identified several novel PTMs that can be removed by sirtuin 4 (SIRT4), which is found in ... Full text Link to item Cite

Metabolic control by sirtuins and other enzymes that sense NAD+, NADH, or their ratio.

Journal Article Biochim Biophys Acta Bioenerg · December 2017 NAD+ is a dinucleotide cofactor with the potential to accept electrons in a variety of cellular reduction-oxidation (redox) reactions. In its reduced form, NADH is a ubiquitous cellular electron donor. NAD+, NADH, and the NAD+/NADH ratio have long been kno ... Full text Link to item Cite

SIRT4 Is a Lysine Deacylase that Controls Leucine Metabolism and Insulin Secretion.

Journal Article Cell Metab · April 4, 2017 Sirtuins are NAD+-dependent protein deacylases that regulate several aspects of metabolism and aging. In contrast to the other mammalian sirtuins, the primary enzymatic activity of mitochondrial sirtuin 4 (SIRT4) and its overall role in metabolic control h ... Full text Link to item Cite

Investigating the Sensitivity of NAD+-dependent Sirtuin Deacylation Activities to NADH.

Journal Article J Biol Chem · March 25, 2016 Protein lysine posttranslational modification by an increasing number of different acyl groups is becoming appreciated as a regulatory mechanism in cellular biology. Sirtuins are class III histone deacylases that use NAD(+)as a co-substrate during amide bo ... Full text Link to item Cite

Sirtuins

Chapter · September 28, 2015 The mammalian sirtuins are a family of seven NAD+-dependent deacetylase enzymes that regulate a wide range of hepatic functions. Altered sirtuin expression in model organisms results in pleiotropic hepatic dysfunction. Furthermore, altered sirtuin expressi ... Full text Cite

SnapShot: Mammalian Sirtuins.

Journal Article Cell · November 6, 2014 The mammalian sirtuins have emerged as critical regulators of cellular stress resistance, energy metabolism, and tumorigenesis. In some contexts, they delay the onset of age-related diseases and promote a healthy lifespan. The seven mammalian sirtuins, SIR ... Full text Link to item Cite

Lysine glutarylation is a protein posttranslational modification regulated by SIRT5.

Journal Article Cell Metab · April 1, 2014 We report the identification and characterization of a five-carbon protein posttranslational modification (PTM) called lysine glutarylation (Kglu). This protein modification was detected by immunoblot and mass spectrometry (MS), and then comprehensively va ... Full text Link to item Cite

Generating mammalian sirtuin tools for protein-interaction analysis.

Journal Article Methods Mol Biol · 2013 The sirtuins are a family of NAD(+)-dependent deacylases with important effects on aging, cancer, and metabolism. Sirtuins exert their biological effects by catalyzing deacetylation and/or deacylation reactions in which Acyl groups are removed from lysine ... Full text Link to item Cite

Deletion of CaMKK2 from the liver lowers blood glucose and improves whole-body glucose tolerance in the mouse.

Journal Article Mol Endocrinol · February 2012 Ca(2+)/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a member of the Ca(2+)/CaM-dependent protein kinase family that is expressed abundantly in brain. Previous work has revealed that CaMKK2 knockout (CaMKK2 KO) mice eat less due to a central ner ... Full text Link to item Cite

Mitochondrial protein acetylation regulates metabolism.

Journal Article Essays Biochem · 2012 Changes in cellular nutrient availability or energy status induce global changes in mitochondrial protein acetylation. Over one-third of all proteins in the mitochondria are acetylated, of which the majority are involved in some aspect of energy metabolism ... Full text Link to item Cite

Characterization of the CaMKKβ-AMPK signaling complex.

Journal Article Cell Signal · December 2011 The AMP-activated protein kinase (AMPK) is a critical regulator of energy homeostasis, and is a potential target for treatment of metabolic diseases as well as cancer. AMPK can be phosphorylated and activated by the tumor suppressor LKB1 or the Ca(2+)/CaM- ... Full text Link to item Cite

BDNF-mediated cerebellar granule cell development is impaired in mice null for CaMKK2 or CaMKIV.

Journal Article J Neurosci · July 15, 2009 The Ca(2+)/calmodulin-activated kinases CaMKK2 and CaMKIV are highly expressed in the brain where they play important roles in activating intracellular responses to elevated Ca(2+). To address the biological functions of Ca(2+) signaling via these kinases ... Full text Link to item Cite

Central control of feeding.

Journal Article F1000 biology reports · January 2009 The rising rate of obesity in Western countries has led to intensified efforts to understand the molecular mechanisms underlying the central control of appetite and feeding behavior. This report highlights studies published from 2006 to 2008 revealing nove ... Full text Cite

Hypothalamic CaMKK2 contributes to the regulation of energy balance.

Journal Article Cell Metab · May 2008 Detailed knowledge of the pathways by which ghrelin and leptin signal to AMPK in hypothalamic neurons and lead to regulation of appetite and glucose homeostasis is central to the development of effective means to combat obesity. Here we identify CaMKK2 as ... Full text Link to item Cite

Regulation of AMP-activated protein kinase by multisite phosphorylation in response to agents that elevate cellular cAMP.

Journal Article J Biol Chem · December 1, 2006 The AMP-activated protein kinase (AMPK) and cAMP signaling systems are both key regulators of cellular metabolism. In this study, we show that AMPK activity is attenuated in response to cAMP-elevating agents through modulation of at least two of its alpha ... Full text Link to item Cite

The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases.

Journal Article J Biol Chem · August 12, 2005 The AMP-activated protein kinase (AMPK) is an important regulator of cellular metabolism in response to metabolic stress and to other regulatory signals. AMPK activity is absolutely dependent upon phosphorylation of AMPKalphaThr-172 in its activation loop ... Full text Link to item Cite

The autonomous activity of calcium/calmodulin-dependent protein kinase IV is required for its role in transcription.

Journal Article J Biol Chem · May 27, 2005 Calcium/calmodulin-dependent kinase IV (CaMKIV) is a multifunctional serine/threonine kinase that is positively regulated by two main events. The first is the binding of calcium/calmodulin (Ca(2+)/CaM), which relieves intramolecular autoinhibition of the e ... Full text Link to item Cite

Statin therapy inhibits fatty acid synthase via dynamic protein modifications.

Journal Article Nat Commun · May 10, 2022 Statins are a class of drug widely prescribed for the prevention of cardiovascular disease, with pleiotropic cellular effects. Statins inhibit HMG-CoA reductase (HMGCR), which converts the metabolite HMG-CoA into mevalonate. Recent discoveries have shown H ... Full text Link to item Cite

Deglutarylation of glutaryl-CoA dehydrogenase by deacylating enzyme SIRT5 promotes lysine oxidation in mice.

Journal Article J Biol Chem · April 2022 A wide range of protein acyl modifications has been identified on enzymes across various metabolic processes; however, the impact of these modifications remains poorly understood. Protein glutarylation is a recently identified modification that can be none ... Full text Link to item Cite

β-Cell-specific ablation of sirtuin 4 does not affect nutrient-stimulated insulin secretion in mice.

Journal Article Am J Physiol Endocrinol Metab · October 1, 2020 Sirtuins are a family of proteins that regulate biological processes such as cellular stress and aging by removing posttranslational modifications (PTMs). We recently identified several novel PTMs that can be removed by sirtuin 4 (SIRT4), which is found in ... Full text Link to item Cite

Metabolic control by sirtuins and other enzymes that sense NAD+, NADH, or their ratio.

Journal Article Biochim Biophys Acta Bioenerg · December 2017 NAD+ is a dinucleotide cofactor with the potential to accept electrons in a variety of cellular reduction-oxidation (redox) reactions. In its reduced form, NADH is a ubiquitous cellular electron donor. NAD+, NADH, and the NAD+/NADH ratio have long been kno ... Full text Link to item Cite

SIRT4 Is a Lysine Deacylase that Controls Leucine Metabolism and Insulin Secretion.

Journal Article Cell Metab · April 4, 2017 Sirtuins are NAD+-dependent protein deacylases that regulate several aspects of metabolism and aging. In contrast to the other mammalian sirtuins, the primary enzymatic activity of mitochondrial sirtuin 4 (SIRT4) and its overall role in metabolic control h ... Full text Link to item Cite

Investigating the Sensitivity of NAD+-dependent Sirtuin Deacylation Activities to NADH.

Journal Article J Biol Chem · March 25, 2016 Protein lysine posttranslational modification by an increasing number of different acyl groups is becoming appreciated as a regulatory mechanism in cellular biology. Sirtuins are class III histone deacylases that use NAD(+)as a co-substrate during amide bo ... Full text Link to item Cite

Sirtuins

Chapter · September 28, 2015 The mammalian sirtuins are a family of seven NAD+-dependent deacetylase enzymes that regulate a wide range of hepatic functions. Altered sirtuin expression in model organisms results in pleiotropic hepatic dysfunction. Furthermore, altered sirtuin expressi ... Full text Cite

SnapShot: Mammalian Sirtuins.

Journal Article Cell · November 6, 2014 The mammalian sirtuins have emerged as critical regulators of cellular stress resistance, energy metabolism, and tumorigenesis. In some contexts, they delay the onset of age-related diseases and promote a healthy lifespan. The seven mammalian sirtuins, SIR ... Full text Link to item Cite

Lysine glutarylation is a protein posttranslational modification regulated by SIRT5.

Journal Article Cell Metab · April 1, 2014 We report the identification and characterization of a five-carbon protein posttranslational modification (PTM) called lysine glutarylation (Kglu). This protein modification was detected by immunoblot and mass spectrometry (MS), and then comprehensively va ... Full text Link to item Cite

Generating mammalian sirtuin tools for protein-interaction analysis.

Journal Article Methods Mol Biol · 2013 The sirtuins are a family of NAD(+)-dependent deacylases with important effects on aging, cancer, and metabolism. Sirtuins exert their biological effects by catalyzing deacetylation and/or deacylation reactions in which Acyl groups are removed from lysine ... Full text Link to item Cite

Deletion of CaMKK2 from the liver lowers blood glucose and improves whole-body glucose tolerance in the mouse.

Journal Article Mol Endocrinol · February 2012 Ca(2+)/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a member of the Ca(2+)/CaM-dependent protein kinase family that is expressed abundantly in brain. Previous work has revealed that CaMKK2 knockout (CaMKK2 KO) mice eat less due to a central ner ... Full text Link to item Cite

Mitochondrial protein acetylation regulates metabolism.

Journal Article Essays Biochem · 2012 Changes in cellular nutrient availability or energy status induce global changes in mitochondrial protein acetylation. Over one-third of all proteins in the mitochondria are acetylated, of which the majority are involved in some aspect of energy metabolism ... Full text Link to item Cite

Characterization of the CaMKKβ-AMPK signaling complex.

Journal Article Cell Signal · December 2011 The AMP-activated protein kinase (AMPK) is a critical regulator of energy homeostasis, and is a potential target for treatment of metabolic diseases as well as cancer. AMPK can be phosphorylated and activated by the tumor suppressor LKB1 or the Ca(2+)/CaM- ... Full text Link to item Cite

BDNF-mediated cerebellar granule cell development is impaired in mice null for CaMKK2 or CaMKIV.

Journal Article J Neurosci · July 15, 2009 The Ca(2+)/calmodulin-activated kinases CaMKK2 and CaMKIV are highly expressed in the brain where they play important roles in activating intracellular responses to elevated Ca(2+). To address the biological functions of Ca(2+) signaling via these kinases ... Full text Link to item Cite

Central control of feeding.

Journal Article F1000 biology reports · January 2009 The rising rate of obesity in Western countries has led to intensified efforts to understand the molecular mechanisms underlying the central control of appetite and feeding behavior. This report highlights studies published from 2006 to 2008 revealing nove ... Full text Cite

Hypothalamic CaMKK2 contributes to the regulation of energy balance.

Journal Article Cell Metab · May 2008 Detailed knowledge of the pathways by which ghrelin and leptin signal to AMPK in hypothalamic neurons and lead to regulation of appetite and glucose homeostasis is central to the development of effective means to combat obesity. Here we identify CaMKK2 as ... Full text Link to item Cite

Regulation of AMP-activated protein kinase by multisite phosphorylation in response to agents that elevate cellular cAMP.

Journal Article J Biol Chem · December 1, 2006 The AMP-activated protein kinase (AMPK) and cAMP signaling systems are both key regulators of cellular metabolism. In this study, we show that AMPK activity is attenuated in response to cAMP-elevating agents through modulation of at least two of its alpha ... Full text Link to item Cite

The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases.

Journal Article J Biol Chem · August 12, 2005 The AMP-activated protein kinase (AMPK) is an important regulator of cellular metabolism in response to metabolic stress and to other regulatory signals. AMPK activity is absolutely dependent upon phosphorylation of AMPKalphaThr-172 in its activation loop ... Full text Link to item Cite

The autonomous activity of calcium/calmodulin-dependent protein kinase IV is required for its role in transcription.

Journal Article J Biol Chem · May 27, 2005 Calcium/calmodulin-dependent kinase IV (CaMKIV) is a multifunctional serine/threonine kinase that is positively regulated by two main events. The first is the binding of calcium/calmodulin (Ca(2+)/CaM), which relieves intramolecular autoinhibition of the e ... Full text Link to item Cite

Regulation and function of the calcium/calmodulin-dependent protein kinase IV/protein serine/threonine phosphatase 2A signaling complex.

Journal Article J Biol Chem · July 23, 2004 Calcium/calmodulin-dependent protein kinase IV (CaMKIV) is a member of the broad substrate specificity class of Ca(2+)/calmodulin (CaM)-dependent protein kinases and functions as a potent stimulator of Ca(2+)-dependent gene expression. Activation of CaMKIV ... Full text Link to item Cite

Catalytic activity is required for calcium/calmodulin-dependent protein kinase IV to enter the nucleus.

Journal Article J Biol Chem · March 19, 2004 Calcium/calmodulin-dependent protein kinase IV (CaMKIV) is a nuclear protein kinase that responds to acute rises in intracellular calcium by phosphorylating and activating proteins involved in transcription. Consistent with these roles, CaMKIV is found pre ... Full text Link to item Cite

Defective signaling in a subpopulation of CD4(+) T cells in the absence of Ca(2+)/calmodulin-dependent protein kinase IV.

Journal Article Mol Cell Biol · January 2002 Ca(2+)/calmodulin-dependent protein kinase IV-deficient (CaMKIV(-/-)) mice have been used to investigate the role of this enzyme in CD4(+) T cells. We identify a functional defect in a subpopulation of CD4(+) T cells, characterized by a cell surface marker ... Full text Link to item Cite

Ca2+/calmodulin-dependent protein kinase IV and calcium signaling.

Journal Article Biometals · December 1998 Ca2+/calmodulin dependent protein kinase IV (CaMKIV) is a multifunctional, serine-threonine protein kinase that is activated in the presence of increased intracellular calcium (Ca2+). CaMKIV is a potent mediator of Ca2+ induced gene expression, primarily t ... Full text Link to item Cite

Components of a calmodulin-dependent protein kinase cascade. Molecular cloning, functional characterization and cellular localization of Ca2+/calmodulin-dependent protein kinase kinase beta.

Journal Article J Biol Chem · November 27, 1998 Ca2+/calmodulin-dependent protein kinases I and IV (CaMKI and CaMKIV, respectively) require phosphorylation on an equivalent single Thr in the activation loop of subdomain VIII for maximal activity. Two distinct CaMKI/IV kinases, CaMKKalpha and CaMKKbeta, ... Full text Link to item Cite

A signaling complex of Ca2+-calmodulin-dependent protein kinase IV and protein phosphatase 2A.

Journal Article Science · May 22, 1998 Stimulation of T lymphocytes results in a rapid increase in intracellular calcium concentration ([Ca2+]i) that parallels the activation of Ca2+-calmodulin-dependent protein kinase IV (CaMKIV), a nuclear enzyme that can phosphorylate and activate the cyclic ... Full text Link to item Cite

Molecular determinants of selectivity in 5-hydroxytryptamine1B receptor-G protein interactions.

Journal Article J Biol Chem · December 19, 1997 The recognition between G protein and cognate receptor plays a key role in specific cellular responses to environmental stimuli. Here we explore specificity in receptor-G protein coupling by taking advantage of the ability of the 5-hydroxytryptamine1B (5-H ... Full text Link to item Cite

Defective survival and activation of thymocytes in transgenic mice expressing a catalytically inactive form of Ca2+/calmodulin-dependent protein kinase IV.

Journal Article Mol Endocrinol · June 1997 We have generated transgenic mice that express a catalytically inactive form of Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) specifically in thymic T cells. The presence of this protein results in a markedly reduced thymic cellularity, although the ... Full text Link to item Cite

Regulation and properties of the rat Ca2+/calmodulin-dependent protein kinase IV gene and its protein products.

Journal Article Recent Prog Horm Res · 1997 Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) is a monomeric multifunctional enzyme that is expressed only in subanatomical portions of the brain, T lymphocytes, and postmeiotic male germ cells. It is present in the nucleus of the cells in which it ... Link to item Cite

Molecular Determinants of Selectivity in Receptor-G protein Interaction

Conference FASEB Journal · January 1, 1997 Helerotrimeric G proteins provide a signal transduction coupling between surface receptors and the effectors that regulate the concentration of the intraccllular second messengers. The specific recognition between G protein and cognate receptor plays a key ... Cite

A unique phosphorylation-dependent mechanism for the activation of Ca2+/calmodulin-dependent protein kinase type IV/GR.

Journal Article J Biol Chem · August 30, 1996 The activity of the Ca2+/calmodulin-dependent protein kinase IV/Gr (CaMKIV/Gr) is shown to be strictly regulated by phosphorylation of three residues both in vitro and in response to antigen receptor-mediated signaling in lymphocytes. One residue, Thr-200, ... Full text Link to item Cite

Multiple Ca(2+)-calmodulin-dependent protein kinase kinases from rat brain. Purification, regulation by Ca(2+)-calmodulin, and partial amino acid sequence.

Journal Article J Biol Chem · May 3, 1996 We have purified to near homogeneity from rat brain two Ca(2+)-calmodulin-dependent protein kinase I (CaM kinase I) activating kinases, termed here CaM kinase I kinase-alpha and CaM kinase I kinase-beta (CaMKIK alpha and CaMKIK beta, respectively). Both Ca ... Full text Link to item Cite

Phosphorylation and activation of Ca(2+)-calmodulin-dependent protein kinase IV by Ca(2+)-calmodulin-dependent protein kinase Ia kinase. Phosphorylation of threonine 196 is essential for activation.

Journal Article J Biol Chem · July 21, 1995 Purified pig brain Ca(2+)-calmodulin (CaM)-dependent protein kinase Ia kinase (Lee, J. C., and Edelman, A. M. (1994) J. Biol. Chem. 269, 2158-2164) enhances, by up to 24-fold, the activity of recombinant CaM kinase IV in a reaction also requiring Ca(2+)-Ca ... Full text Link to item Cite

T-tubule depolarization-induced SR Ca2+ release is controlled by dihydropyridine receptor- and Ca(2+)-dependent mechanisms in cell homogenates from rabbit skeletal muscle.

Journal Article J Gen Physiol · March 1995 In vertebrate skeletal muscle, the voltage-dependent mechanism of rapid sarcoplasmic reticulum (SR) Ca2+ release, commonly referred to as excitation-contraction (EC) coupling, is believed to be mediated by physical interaction between the transverse (T)-tu ... Full text Link to item Cite

High-affinity [3H]PN200-110 and [3H]ryanodine binding to rabbit and frog skeletal muscle.

Journal Article Am J Physiol · February 1994 In vertebrate skeletal muscle, the voltage-dependent mechanism of sarcoplasmic reticulum (SR) Ca2+ release, commonly referred to as excitation-contraction (E-C) coupling, is mediated by the voltage-sensing dihydropyridine receptor (DHPR), which is believed ... Full text Link to item Cite

Effects of perchlorate on the molecules of excitation-contraction coupling of skeletal and cardiac muscle.

Journal Article J Gen Physiol · September 1993 To understand the nature of the transmission process of excitation-contraction (EC) coupling, the effects of the anion perchlorate were investigated on the voltage sensor (dihydropyridine receptor, DHPR) and the Ca release channel (ryanodine receptor, RyR) ... Full text Link to item Cite

Structural and functional characterization of the purified cardiac ryanodine receptor-Ca2+ release channel complex.

Journal Article J Biol Chem · January 15, 1989 Using density gradient centrifugation and [3H]ryanodine as a specific marker, the ryanodine receptor-Ca2+ release channel complex from Chaps-solubilized canine cardiac sarcoplasmic reticulum (SR) has been purified in the form of an approximately 30 S compl ... Link to item Cite

Evidence for a Ca2+ channel within the ryanodine receptor complex from cardiac sarcoplasmic reticulum.

Journal Article Biochem Biophys Res Commun · February 29, 1988 The solubilized [3H]ryanodine receptor from cardiac sarcoplasmic reticulum was centrifuged through linear sucrose gradients. A single peak of radioactivity with apparent sedimentation coefficient of approximately 30S specifically comigrated with a high mol ... Full text Link to item Cite

Biochemical characterization of the Ca2+ release channel of skeletal and cardiac sarcoplasmic reticulum.

Journal Article Mol Cell Biochem · 1988 Rapid mixing-vesicle ion flux and planar lipid bilayer-single channel measurements have shown that a high-conductance, ligand-gated Ca2+ release channel is present in 'heavy', junctional-derived membrane fractions of skeletal and cardiac muscle sarcoplasmi ... Full text Link to item Cite