Human T-cell leukemia virus oncoprotein Tax represses nuclear receptor-dependent transcription by targeting coactivator TAX1BP1

Human T-cell leukemia virus type 1 oncoprotein Tax is a transcriptional regulator that interacts with a large number of host cell factors. Here, we report the novel characterization of the interaction of Tax with a human cell protein named Tax1-binding protein 1 (TAX1BP1). We show that TAX1BP1 is a nuclear receptor coactivator that forms a complex with the glucocorticoid receptor. TAX1BP1 and Tax colocalize into intranuclear speckles that partially overlap with but are not identical to the PML oncogenic domains. Tax binds TAX1BP1 directly, induces the dissociation of TAX1BP1 from the glucocorticoid receptor-containing protein complex, and represses the coactivator function of TAX1BP1. Genetic knockout of Tax1bp1 in mice abrogates the influence of Tax on the activation of nuclear receptors. We propose that Tax-TAX1BP1 interaction mechanistically explains the previously reported repression of nuclear receptor activity by Tax. ©2007 American Association for Cancer Research.postprin

Differential subcellular localization and activity of kelch repeat proteins KLHDC1 and KLHDC2.

We have previously identified and characterized human KLHDC2/HCLP-1, a kelch repeat protein that interacts with and inhibits transcription factor LZIP. In this study, we identified and characterized a paralog of KLHDC2 called KLHDC1. KLHDC1 and KLHDC2 share about 50% identity at the level of amino acid sequence and both gene loci localize to human chromosome 14q21.3. This cluster of KLHDC1 and KLHDC2 genes is highly conserved in vertebrates ranging from pufferfish to human. Both genes are expressed highly in skeletal muscle, but weakly in various other tissues. While KLHDC2 was predominantly found in the nucleus, KLHDC1 is a cytoplasmic protein. Neither KLHDC1 nor KLHDC2 binds to actin. In addition, KLHDC1 was unable to inhibit LZIP/CREB3-mediated transcriptional activation. Thus, KLHDC1 and KLHDC2 have differential localization and activity in cultured mammalian cells.postprin

Functional characterization of liver-enriched transcription factor CREB-H (poster 1989)

Tissue-Specific Gene Expression (1985-2002) Sessionpublished_or_final_versio

Functional characterization of the liver-enriched transcription factor CREB-H

Session - Tissue-Specific Gene Expression (1985-2002)postprin

An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly

Erythropoetin-producing hepatoma (Eph) receptors are cell-surface protein tyrosine kinases mediating cell-cell communication. Upon activation, they form signaling clusters. We report crystal structures of the full ectodomain of human EphA2 (eEphA2) both alone and in complex with the receptor-binding domain of the ligand ephrinA5 (ephrinA5 RBD). Unliganded eEphA2 forms linear arrays of staggered parallel receptors involving two patches of residues conserved across A-class Ephs. eEphA2-ephrinA5 RBD forms a more elaborate assembly, whose interfaces include the same conserved regions on eEphA2, but rearranged to accommodate ephrinA5 RBD. Cell-surface expression of mutant EphA2s showed that these interfaces are critical for localization at cell-cell contacts and activation-dependent degradation. Our results suggest a 'nucleation' mechanism whereby a limited number of ligand-receptor interactions 'seed' an arrangement of receptors which can propagate into extended signaling arrays

Nutritional concerns, health and survival in old age

The ageing process is—apart from chance or good luck—not only influenced by factors intrinsic to the individual, but also by extrinsic factors that include environmental and lifestyle variables. This paper deals with the epidemiological evidence for the role of dietary patterns and key nutritional concerns in relation to survival and ageing related disorders that present themselves in later life. Dietary patterns, such as the Mediterranean diet, characterized by mainly plant foods including protective factors e.g. vegetables, nuts and monounsaturated fatty acids and excluding harmful factors e.g. trans-fatty acids and foods with a high glycemic factor, appear to be relevant even in old age. Specific nutritional concerns focus on general undernutrition, vitamin D and vitamin B12. Prevalence of nutritional inadequacies, diagnostic criteria, causes and health consequences are described. The paper ends with recommendations for guidance on healthy diets for elderly people. An important challenge should be research to further expand the knowledge base, acknowledging the complexity of the ageing process and integrating different dimensions of research into human healthy ageing in properly designed studies. In the mean time reversing poor adherence to existing guidelines for a healthy diet remains a first challenge in public health nutritional practices

Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.

BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721

Disease burden and related medical costs of rotavirus infections in Taiwan

BACKGROUND: The disease burden and associated medical costs of rotavirus infections in inpatient and outpatient sectors in Taiwan were examined in anticipation of the availability of new rotavirus vaccines. METHODS: The yearly national case number and medical costs for all for inpatients and outpatients with acute gastroenteritis (AGE) were extracted from the Bureau of National Health Insurance database in Taiwan according to ICD-9-CM codes. A retrospective study was also performed using records of children with AGE seen at three hospitals in Taiwan in 2001 to identify laboratory confirmed rotavirus infection cases. The annual incidence and related medical costs of AGE due to rotavirus infection were then estimated. RESULTS: Children <5 years old comprised 83.6% of inpatient and 62.0% of outpatient pediatric AGE cases in Taiwan in 2001. Rotavirus was the most common agent detected among AGE patients in this age group in the three hospitals, and was detected in 32.9% (221/672) of inpatient and 24% (23/96) of outpatient stool specimens tested for microbial etiologies. An estimated 277,400 to 624,892 cases of rotavirus infections sought medical care in Taiwan in 2001, equaling one in 2 to 5 children <5 years old required medical care due to rotavirus infection. The incidence of hospitalization due to rotavirus infections was 1,528–1,997/100,000 for children <5 years old. The total associated medical costs due to rotavirus infection were estimated at US $10–16 millions in Taiwan in 2001. Although the per-capita medical cost of rotavirus infection was lower in Taiwan than in the United States or Hong Kong, the personal economic burden was similar among the three places when normalized for gross national incomes per capita. CONCLUSION: Infections caused by rotavirus constitute an important human and economic burden among young children in Taiwan. A safe and effective vaccine is urgently needed