Galy Flores | Universidad Tecnológica de El Salvador (original) (raw)

Papers by Galy Flores

Research paper thumbnail of Mechanism of Ubiquitin Recognition by the CUE Domain of Vps9p

Cell, 2003

Many ubiquitinated proteins are recognized by do-200 First Street SW mains that specifically bind... more Many ubiquitinated proteins are recognized by do-200 First Street SW mains that specifically bind to mono-and/or polyubiqui-Rochester, Minnesota 55905 tin. These include the UEV, UBA, UIM, and CUE domains or motifs (reviewed in Buchberger, 2002). The UEV domain is a counterpart of a ubiquitin-conjugating enzyme, Summary as illustrated by the structure of the enzymatically inactive TSG101 UEV domain (Pornillos et al., 2002). The Coupling of ubiquitin conjugation to ER degradation other three prominent ubiquitin binding domains, UBA, (CUE) domains are ‫05ف‬ amino acid monoubiquitin UIM, and CUE, are all small (20-50 amino acids) and are binding motifs found in proteins of trafficking and ubiknown or predicted to be ␣-helical. The ubiquitin binding quitination pathways. The 2.3 Å structure of the Vps9p-UBA domain is found in DNA damage-inducible and CUE domain is a dimeric domain-swapped variant of other proteins (Hofmann and Bucher, 1996). UBA dothe ubiquitin binding UBA domain. The 1.7 Å structure mains are three-helix bundles (Dieckmann et al., 1998; of the CUE:ubiquitin complex shows that one CUE Withers-Ward et al., 2000; Mueller and Feigon, 2002) dimer binds one ubiquitin molecule. The bound CUE that can bind polyubiquitin with high affinity, and their dimer is kinked relative to the unbound CUE dimer physiological functioning is in at least some cases mediand wraps around ubiquitin. The CUE monomer conated by polyubiquitin binding (Wilkinson et al., 2001; tains two ubiquitin binding surfaces on opposite faces Funakoshi et al., 2002). UBA domains also bind monoof the molecule that cannot bind simultaneously to ubiquitin (Vadlamudi et al., 1996; Bertolaet et al., 2001b; a single ubiquitin molecule. Dimerization of the CUE Chen et al., 2001), bind to other proteins (Dieckmann et domain allows both surfaces to contact a single ubial., 1998; Withers-Ward et al., 2000), and form homoquitin molecule, providing a mechanism for high-affinand heterodimers with each other (Bertolaet et al., ity binding to monoubiquitin. 2001a). The UIM (ubiquitin interaction motif; Hofmann and Falquet, 2001) is a ubiquitin binding motif discov-Introduction ered in the proteasome subunit S5a. The S5a UIM binds polyubiquitin, but not monoubiquitin (Deveraux et al., The covalent addition of ubiquitin and ubiquitin-like pro-1994). In contrast, UIMs of many endocytic proteins bind teins is one of the most widespread regulatory postmonoubiquitinated proteins. The endocytic proteins eptranslational modifications of proteins (Hershko and Ciesin, eps15, Vps27p/Hrs, and Hse1p contain UIMs that chanover, 1998; Hochstrasser, 2000; Pickart, 2001). bind monoubiquitin (Bilodeau et al., 2002; Klapisz et al., Ubiquitin is a 76 amino acid protein named for its ex-2002; Oldham et al., 2002; Polo et al., 2002; Raiborg et traordinary distribution from yeast to man. The C termial., 2002; Shih et al., 2002; Shekhtman and Cowburn, nus of ubiquitin is conjugated to Lys residues of target 2002). The UIMs of eps15 are essential for the ubiquitinaproteins by the action of three enzymes: an ubiquitintion of eps15 itself, representing a second function for activating enzyme (E1), an ubiquitin-conjugating en-UIMs in promoting the ubiquitination of proteins that zyme (E2), and an ubiquitin protein ligase (E3). contain them (Polo et al., 2002). Ubiquitin is conjugated to proteins via an isopeptide The most recent addition to the family of ubiquitin bond between the C terminus of ubiquitin and a specific binding domains is the coupling of ubiquitin conjugation Lys residue in the ubiquitinated protein. Ubiquitin may to ER degradation (CUE) domain, which is found in roughly 50 different proteins (Ponting, 2000, 2002; Batebe attached to proteins as a monomer or as a polyubiquiman et al., 2002). CUE domains are named for the yeast tin chain. Ubiquitin polymers are formed when additional Cue1p protein, which recruits the ubiquitin-conjugating ubiquitin molecules are attached to Lys residues on a enzyme Ubc7p to the ER, where it is essential for misfolded protein degradation (Biederer et al., 1997). Other *Correspondence: james.hurley@nih.gov CUE domain proteins include the autocrine motility fac-3 These authors contributed equally to this work. tor receptor (AMFR), a ubiquitin protein ligase also in-4 Present address: Laboratory of Biochemistry, National Cancer Institute, Bethesda, Maryland 20892. volved in protein degradation at the ER (Fang et al., Deveraux, Q., Ustrell, V., Pickart, C., and Rechsteiner, M. (1994). A 26 S protease subunit that binds ubiquitin conjugates. J. Biol. Chem. 269, 7059-7061. We thank B. Beach for DNA sequencing, A. Hickman for critical comments on the manuscript, G. Miller and R. Trievel for assistance Dieckmann, T., Withers-Ward, E.S., Jarosinksi, M.A., Liu, C.-F., with data collection, and A. Weissman for discussions. This study Chen, I.S.Y., and Feigon, J. (1998). Structure of a human DNA repair was supported in part by NIH grant number GM55301 to B.F.H. and protein UBA domain that interacts with HIV-1 Vpr. Nat. Struct. Biol. a predoctoral fellowship from the HHMI to B.A.D. We acknowledge 5, 1042-1047. use of the SBC-CAT and SER-CAT beamlines at the APS, ANL.

Research paper thumbnail of Consumption and housing wealth breakdown of the effect of a rise in interest rates

Applied Economics, 2011

In this article the effect on consumption of a fall in housing wealth and housing prices, resulti... more In this article the effect on consumption of a fall in housing wealth and housing prices, resulting from an increase in interest rates is estimated. With the help of a dynamic multiequation, macroeconomic model, the consumer response function is broken down into two parts: a direct response related to a rise in the cost of credit and another indirect one related to the deterioration of the property market. Estimation of the theoretical model is done by means of a Vectorial Error-Correction (VEC) model.

Research paper thumbnail of Consumption and housing wealth breakdown of the effect of a rise in interest rates

Applied Economics, 2012

In this article the effect on consumption of a fall in housing wealth and housing prices, resulti... more In this article the effect on consumption of a fall in housing wealth and housing prices, resulting from an increase in interest rates is estimated. With the help of a dynamic multiequation, macroeconomic model, the consumer response function is broken down into two parts: a direct response related to a rise in the cost of credit and another indirect one related to the deterioration of the property market. Estimation of the theoretical model is done by means of a Vectorial Error-Correction (VEC) model.

Research paper thumbnail of Guidelines for the use and interpretation of assays for monitoring autophagy

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since t... more In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

Research paper thumbnail of La contabilidad y el sistema contable Indice

La contabilidad y el sistema contable Indice 1. Introducción 2. Concepto De Contabilidad 3. Evolu... more La contabilidad y el sistema contable Indice 1. Introducción 2. Concepto De Contabilidad 3. Evolución de la contabilidad y sus principales aportes. 4. Estructura de un sistema contable 5. Objetivos de la información contable. 6. Conclusión

Research paper thumbnail of Mechanism of Ubiquitin Recognition by the CUE Domain of Vps9p

Cell, 2003

Many ubiquitinated proteins are recognized by do-200 First Street SW mains that specifically bind... more Many ubiquitinated proteins are recognized by do-200 First Street SW mains that specifically bind to mono-and/or polyubiqui-Rochester, Minnesota 55905 tin. These include the UEV, UBA, UIM, and CUE domains or motifs (reviewed in Buchberger, 2002). The UEV domain is a counterpart of a ubiquitin-conjugating enzyme, Summary as illustrated by the structure of the enzymatically inactive TSG101 UEV domain (Pornillos et al., 2002). The Coupling of ubiquitin conjugation to ER degradation other three prominent ubiquitin binding domains, UBA, (CUE) domains are ‫05ف‬ amino acid monoubiquitin UIM, and CUE, are all small (20-50 amino acids) and are binding motifs found in proteins of trafficking and ubiknown or predicted to be ␣-helical. The ubiquitin binding quitination pathways. The 2.3 Å structure of the Vps9p-UBA domain is found in DNA damage-inducible and CUE domain is a dimeric domain-swapped variant of other proteins (Hofmann and Bucher, 1996). UBA dothe ubiquitin binding UBA domain. The 1.7 Å structure mains are three-helix bundles (Dieckmann et al., 1998; of the CUE:ubiquitin complex shows that one CUE Withers-Ward et al., 2000; Mueller and Feigon, 2002) dimer binds one ubiquitin molecule. The bound CUE that can bind polyubiquitin with high affinity, and their dimer is kinked relative to the unbound CUE dimer physiological functioning is in at least some cases mediand wraps around ubiquitin. The CUE monomer conated by polyubiquitin binding (Wilkinson et al., 2001; tains two ubiquitin binding surfaces on opposite faces Funakoshi et al., 2002). UBA domains also bind monoof the molecule that cannot bind simultaneously to ubiquitin (Vadlamudi et al., 1996; Bertolaet et al., 2001b; a single ubiquitin molecule. Dimerization of the CUE Chen et al., 2001), bind to other proteins (Dieckmann et domain allows both surfaces to contact a single ubial., 1998; Withers-Ward et al., 2000), and form homoquitin molecule, providing a mechanism for high-affinand heterodimers with each other (Bertolaet et al., ity binding to monoubiquitin. 2001a). The UIM (ubiquitin interaction motif; Hofmann and Falquet, 2001) is a ubiquitin binding motif discov-Introduction ered in the proteasome subunit S5a. The S5a UIM binds polyubiquitin, but not monoubiquitin (Deveraux et al., The covalent addition of ubiquitin and ubiquitin-like pro-1994). In contrast, UIMs of many endocytic proteins bind teins is one of the most widespread regulatory postmonoubiquitinated proteins. The endocytic proteins eptranslational modifications of proteins (Hershko and Ciesin, eps15, Vps27p/Hrs, and Hse1p contain UIMs that chanover, 1998; Hochstrasser, 2000; Pickart, 2001). bind monoubiquitin (Bilodeau et al., 2002; Klapisz et al., Ubiquitin is a 76 amino acid protein named for its ex-2002; Oldham et al., 2002; Polo et al., 2002; Raiborg et traordinary distribution from yeast to man. The C termial., 2002; Shih et al., 2002; Shekhtman and Cowburn, nus of ubiquitin is conjugated to Lys residues of target 2002). The UIMs of eps15 are essential for the ubiquitinaproteins by the action of three enzymes: an ubiquitintion of eps15 itself, representing a second function for activating enzyme (E1), an ubiquitin-conjugating en-UIMs in promoting the ubiquitination of proteins that zyme (E2), and an ubiquitin protein ligase (E3). contain them (Polo et al., 2002). Ubiquitin is conjugated to proteins via an isopeptide The most recent addition to the family of ubiquitin bond between the C terminus of ubiquitin and a specific binding domains is the coupling of ubiquitin conjugation Lys residue in the ubiquitinated protein. Ubiquitin may to ER degradation (CUE) domain, which is found in roughly 50 different proteins (Ponting, 2000, 2002; Batebe attached to proteins as a monomer or as a polyubiquiman et al., 2002). CUE domains are named for the yeast tin chain. Ubiquitin polymers are formed when additional Cue1p protein, which recruits the ubiquitin-conjugating ubiquitin molecules are attached to Lys residues on a enzyme Ubc7p to the ER, where it is essential for misfolded protein degradation (Biederer et al., 1997). Other *Correspondence: james.hurley@nih.gov CUE domain proteins include the autocrine motility fac-3 These authors contributed equally to this work. tor receptor (AMFR), a ubiquitin protein ligase also in-4 Present address: Laboratory of Biochemistry, National Cancer Institute, Bethesda, Maryland 20892. volved in protein degradation at the ER (Fang et al., Deveraux, Q., Ustrell, V., Pickart, C., and Rechsteiner, M. (1994). A 26 S protease subunit that binds ubiquitin conjugates. J. Biol. Chem. 269, 7059-7061. We thank B. Beach for DNA sequencing, A. Hickman for critical comments on the manuscript, G. Miller and R. Trievel for assistance Dieckmann, T., Withers-Ward, E.S., Jarosinksi, M.A., Liu, C.-F., with data collection, and A. Weissman for discussions. This study Chen, I.S.Y., and Feigon, J. (1998). Structure of a human DNA repair was supported in part by NIH grant number GM55301 to B.F.H. and protein UBA domain that interacts with HIV-1 Vpr. Nat. Struct. Biol. a predoctoral fellowship from the HHMI to B.A.D. We acknowledge 5, 1042-1047. use of the SBC-CAT and SER-CAT beamlines at the APS, ANL.

Research paper thumbnail of Consumption and housing wealth breakdown of the effect of a rise in interest rates

Applied Economics, 2011

In this article the effect on consumption of a fall in housing wealth and housing prices, resulti... more In this article the effect on consumption of a fall in housing wealth and housing prices, resulting from an increase in interest rates is estimated. With the help of a dynamic multiequation, macroeconomic model, the consumer response function is broken down into two parts: a direct response related to a rise in the cost of credit and another indirect one related to the deterioration of the property market. Estimation of the theoretical model is done by means of a Vectorial Error-Correction (VEC) model.

Research paper thumbnail of Consumption and housing wealth breakdown of the effect of a rise in interest rates

Applied Economics, 2012

In this article the effect on consumption of a fall in housing wealth and housing prices, resulti... more In this article the effect on consumption of a fall in housing wealth and housing prices, resulting from an increase in interest rates is estimated. With the help of a dynamic multiequation, macroeconomic model, the consumer response function is broken down into two parts: a direct response related to a rise in the cost of credit and another indirect one related to the deterioration of the property market. Estimation of the theoretical model is done by means of a Vectorial Error-Correction (VEC) model.

Research paper thumbnail of Guidelines for the use and interpretation of assays for monitoring autophagy

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since t... more In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

Research paper thumbnail of La contabilidad y el sistema contable Indice

La contabilidad y el sistema contable Indice 1. Introducción 2. Concepto De Contabilidad 3. Evolu... more La contabilidad y el sistema contable Indice 1. Introducción 2. Concepto De Contabilidad 3. Evolución de la contabilidad y sus principales aportes. 4. Estructura de un sistema contable 5. Objetivos de la información contable. 6. Conclusión