Dataset Information

A reversible form of lysine acetylation in the ER and Golgi lumen controls the molecular stabilization of BACE1.

ABSTRACT: The lipid second messenger ceramide regulates the rate of beta cleavage of the Alzheimer's disease APP (amyloid precursor protein) by affecting the molecular stability of the beta secretase BACE1 (beta-site APP cleaving enzyme 1). Such an event is stimulated in the brain by the normal process of aging, and is under the control of the general aging programme mediated by the insulin-like growth factor 1 receptor. In the present study we report that BACE1 is acetylated on seven lysine residues of the N-terminal portion of the nascent protein. This process involves lysine acetylation in the lumen of the ER (endoplasmic reticulum) and is followed by deacetylation in the lumen of the Golgi apparatus, once the protein is fully mature. We also show that specific enzymatic activities acetylate (in the ER) and deacetylate (in the Golgi apparatus) the lysine residues. This process requires carrier-mediated translocation of acetyl-CoA into the ER lumen and is stimulated by ceramide. Site-directed mutagenesis indicates that lysine acetylation is necessary for nascent BACE1 to leave the ER and move ahead in the secretory pathway, and for the molecular stabilization of the protein.

SUBMITTER: Costantini C

PROVIDER: S-EPMC2275071 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A reversible form of lysine acetylation in the ER and Golgi lumen controls the molecular stabilization of BACE1.

Costantini Claudio C Ko Mi Hee MH Jonas Mary Cabell MC Puglielli Luigi L

The Biochemical journal 20071101 3

The lipid second messenger ceramide regulates the rate of beta cleavage of the Alzheimer's disease APP (amyloid precursor protein) by affecting the molecular stability of the beta secretase BACE1 (beta-site APP cleaving enzyme 1). Such an event is stimulated in the brain by the normal process of aging, and is under the control of the general aging programme mediated by the insulin-like growth factor 1 receptor. In the present study we report that BACE1 is acetylated on seven lysine residues of t ...[more]

PMID: 17425515

Similar Datasets

Project description:UnlabelledIn Salmonella enterica, the reversible lysine acetylation (RLA) system is comprised of the protein acetyltransferase (Pat) and sirtuin deacetylase (CobB). RLA controls the activities of many proteins, including the acetyl coenzyme A (acetyl-CoA) synthetase (Acs), by modulating the degree of Acs acetylation. We report that IolR, a myo-inositol catabolism repressor, activates the expression of genes encoding components of the RLA system. In vitro evidence shows that the IolR protein directly regulates pat expression. An iolR mutant strain displayed a growth defect in minimal medium containing 10 mM acetate, a condition under which RLA function is critical to control Acs activity. Increased levels of Pat, CobB, or Acs activity reversed the growth defect, suggesting the Pat/CobB ratio in an iolR strain is altered and that such a change affects the level of acetylated, inactive Acs. Results of quantitative reverse transcription-PCR (qRT-PCR) analyses of pat, cobB, and acs expression indicated that expression of the genes alluded to in the IolR-deficient strain was reduced 5-, 3-, and 2.6-fold, respectively, relative to the levels present in the strain carrying the iolR(+) allele. Acs activity in cell-free extracts from an iolR mutant strain was reduced ~25% relative to that of the iolR(+) strain. Glucose differentially regulated expression of pat, cobB, and acs. The catabolite repressor protein (Crp) positively regulated expression of pat while having no effect on cobB.ImportanceReversible lysine acylation is used by cells of all domains of life to modulate the function of proteins involved in diverse cellular processes. Work reported herein begins to outline the regulatory circuitry that integrates the expression of genes encoding enzymes that control the activity of a central metabolic enzyme in C2 metabolism. Genetic analyses revealed effects on reversible lysine acylation that greatly impacted the growth behavior of the cell. This work provides the first insights into the complexities of the system responsible for controlling reversible lysine acylation at the transcriptional level in the enteropathogenic bacterium Salmonella enterica.

Dataset Information

A reversible form of lysine acetylation in the ER and Golgi lumen controls the molecular stabilization of BACE1.

Publications

A reversible form of lysine acetylation in the ER and Golgi lumen controls the molecular stabilization of BACE1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets