No abstract

Purine catabolic pathway in Bacillus subtilis is consisted of more than 14 genes. Among these genes, pucL and pucM are required for uricase activity. While PucL is known to encode the uricase itself, the function of PucM is still unclear although this protein is also indispensable for uric acid decomposition. Here, we provide evidence that PucM, a transthyretin-related protein, functions to facilitate the hydrolysis of 5-hydroxyisourate, the end product of the uricase reaction. Based on these results, we propose that transthyretin-related proteins present in diverse organisms are not functionally related to transthyretin but actually function as a hydroxyisourate hydrolase.

This article is available online at http://www.jlr.org deacetylases (HDACs) and histone acetyltransferases are enzymes that catalyze deacetylation and acetylation of the -amino groups of lysine residues of proteins. Lysine acetylation was fi rst discovered to occur in histones, and histone acetylation is important in controlling the structure and function of chromatin ( 1 ). A large number of studies have further shown the existence of acetylated nonhistone proteins, including transcription factors, hormone receptors, signal transducers, and chaperones. The reversible acetylation of nonhistone proteins modulates a wide variety of key cellular processes, such as apoptosis, survival, and proliferation. Recently, several groups have reported that many metabolic enzymes are highly acetylated ( 2-5 ). Such enzymes are involved in glycolysis, fatty acid metabolism, gluconeogenesis, the TCA cycle, and the urea cycle, and the acetylation of these proteins regulates their activity so that they can respond to the metabolic demands of cells.Adipose tissue, which consists of loose connective tissue composed of adipocytes, is an important metabolic organ that functions in energy homeostasis ( 6 ). Adipocytes regulate physiologic processes, including glucose metabolism, angiogenesis, the infl ammatory response, and reproductive functions through secreted adipokines. Adipocyte differentiation can contribute to the development of obesity via a positive energy balance (energy intake > energy expenditure) ( 7 ). Obesity leads to serious health problems all over the world. The coexistence of obesity, type II diabetes, dyslipidemia, and hypertension, known as metabolic syndrome, constitutes an increased risk for the development of cardiovascular diseases ( 8 ). In adipocytes, fatty acids are stored as triglycerides, which serve as the fuel for maintaining energy balance. Acetyl-CoA is the direct precursor in the synthesis of fatty acids, and all fatty acid carbons come from the acetyl group of acetyl-CoA. In addition, it has Abstract Acetylation is one of the most crucial posttranslational modifi cations that affect protein function. Protein lysine acetylation is catalyzed by acetyltransferases, and acetyl-CoA functions as the source of the acetyl group. Additionally, acetyl-CoA plays critical roles in maintaining the balance between carbohydrate metabolism and fatty acid synthesis. Here, we sought to determine whether lysine acetylation is an important process for adipocyte differentiation. Based on an analysis of the acetylome during adipogenesis, various proteins displaying signifi cant quantitative changes were identifi ed by LC-MS/MS. Of these identifi ed proteins, we focused on malate dehydrogenase 1 (MDH1). The acetylation level of MDH1 was increased up to 6-fold at the late stage of adipogenesis. Moreover, overexpression of MDH1 in 3T3-L1 preadipocytes induced a signifi cant increase in the number of cells undergoing adipogenesis. The introduction of mutations to putative lysine acetylation sites showed a signifi cant loss ...

(2003). Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKB beta.

Previously, we identified annexin A4 (ANXA4) as a candidate substrate of caspase-3. Proteomic studies were performed to identify interacting proteins with a view to determining the roles of ANXA4. ANXA4 was found to interact with the p105. Subsequent studies revealed that ANXA4 interacts with NF-kappaB through the Rel homology domain of p50. Furthermore, the interaction is markedly increased by elevated Ca(2+) levels. NF-kappaB transcriptional activity assays demonstrated that ANXA4 suppresses NF-kappaB transcriptional activity in the resting state. Following treatment with TNF-alpha or PMA, ANXA4 also suppressed NF-kappaB transcriptional activity, which was upregulated significantly early after etoposide treatment. This difference may be due to the intracellular Ca(2+) level. Additionally, ANXA4 translocates to the nucleus together with p50, and imparts greater resistance to apoptotic stimulation by etoposide. Our results collectively indicate that ANXA4 differentially modulates the NF-kappaB signaling pathway, depending on its interactions with p50 and the intracellular Ca(2+) ion level.