Abstract:
:Adequate lipid secretion by mammary glands during lactation is essential for the survival of mammalian offspring. However, the mechanism governing this process is poorly understood. Here we show that Cidea is expressed at high levels in lactating mammary glands and its deficiency leads to premature pup death as a result of severely reduced milk lipids. Furthermore, the expression of xanthine oxidoreductase (XOR), an essential factor for milk lipid secretion, is markedly lower in Cidea-deficient mammary glands. Conversely, ectopic Cidea expression induces the expression of XOR and enhances lipid secretion in vivo. Unexpectedly, as Cidea has heretofore been thought of as a cytoplasmic protein, we detected it in the nucleus and found it to physically interact with transcription factor CCAAT/enhancer-binding protein β (C/EBPβ) in mammary epithelial cells. We also observed that Cidea induces XOR expression by promoting the association of C/EBPβ onto, and the dissociation of HDAC1 from, the promoter of the Xdh gene encoding XOR. Finally, we found that Fsp27, another CIDE family protein, is detected in the nucleus and interacts with C/EBPβ to regulate expression of a subset of C/EBPβ downstream genes in adipocytes. Thus, Cidea acts as a previously unknown transcriptional coactivator of C/EBPβ in mammary glands to control lipid secretion and pup survival.
journal_name
Nat Medjournal_title
Nature medicineauthors
Wang W,Lv N,Zhang S,Shui G,Qian H,Zhang J,Chen Y,Ye J,Xie Y,Shen Y,Wenk MR,Li Pdoi
10.1038/nm.2614subject
Has Abstractpub_date
2012-01-15 00:00:00pages
235-43issue
2eissn
1078-8956issn
1546-170Xpii
nm.2614journal_volume
18pub_type
杂志文章相关文献
NATURE MEDICINE文献大全abstract::We report the involvement of an evolutionarily conserved set of mycobacterial genes, the esx-3 region, in evasion of bacterial killing by innate immunity. Whereas high-dose intravenous infections of mice with the rapidly growing mycobacterial species Mycobacterium smegmatis bearing an intact esx-3 locus were rapidly l...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.2420
更新日期:2011-09-04 00:00:00
abstract::Idiopathic voiding disorders affect up to 10-15% of men and women. We describe bladder abnormalities in mice with targeted deletion of the gene for neuronal nitric oxide synthase which model the clinical disorders. The mice possess hypertrophic dilated bladders and dysfunctional urinary outlets which do not relax in r...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0597-571
更新日期:1997-05-01 00:00:00
abstract::The identification of the genes associated with chromosomal translocation breakpoints has fundamentally changed understanding of the molecular basis of hematological malignancies. By contrast, the study of chromosomal deletions has been hampered by the large number of genes deleted and the complexity of their analysis...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.2063
更新日期:2010-01-01 00:00:00
abstract::Huntington's disease is caused by an expanded polyglutamine repeat in the huntingtin protein (HTT), but the pathophysiological sequence of events that trigger synaptic failure and neuronal loss are not fully understood. Alterations in N-methyl-D-aspartate (NMDA)-type glutamate receptors (NMDARs) have been implicated. ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3246
更新日期:2013-08-01 00:00:00
abstract::Oxidative damage from elevated production of reactive oxygen species (ROS) contributes to ischemia-reperfusion injury in myocardial infarction and stroke. The mechanism by which the increase in ROS occurs is not known, and it is unclear how this increase can be prevented. A wide variety of nitric oxide donors and S-ni...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3212
更新日期:2013-06-01 00:00:00
abstract::In many areas of oncology, we lack sensitive tools to track low-burden disease. Although cell-free DNA (cfDNA) shows promise in detecting cancer mutations, we found that the combination of low tumor fraction (TF) and limited number of DNA fragments restricts low-disease-burden monitoring through the prevailing deep ta...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-020-0915-3
更新日期:2020-07-01 00:00:00
abstract::A characteristic feature of Creutzfeldt-Jakob disease (CJD) is the accumulation in the brain of the amyloid protease-resistant protein PrPres. PrPres derives from a host-encoded, protease-sensitive isoform, PrPsen. Mutations of this protein are linked to familial variants of the disease, and the presence of a methioni...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0597-521
更新日期:1997-05-01 00:00:00
abstract::Transforming growth factor beta 1 (TGF-beta 1) is a platelet-derived cytokine involved in both normal wound healing and scarring. We show that human platelets contain two pools of latent TGF-beta 1, which constitute more than 95% of the total TGF-beta assayed in whole platelets. During clotting, one pool, the large la...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0995-932
更新日期:1995-09-01 00:00:00
abstract::Cellular immunity has an inherent high level of functional heterogeneity. Capturing the full spectrum of these functions requires analysis of large numbers of effector molecules from single cells. We report a microfluidic platform designed for highly multiplexed (more than ten proteins), reliable, sample-efficient (∼1...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.2375
更新日期:2011-06-01 00:00:00
abstract::While investigating the novel anticancer drug ecteinascidin 743 (Et743), a natural marine product isolated from the Caribbean sea squirt, we discovered a new cell-killing mechanism mediated by DNA nucleotide excision repair (NER). A cancer cell line selected for resistance to Et743 had chromosome alterations in a regi...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/91008
更新日期:2001-08-01 00:00:00
abstract::Cystinuria is an incompletely dominant disorder characterized by defective urinary cystine reabsorption that results in the formation of cystine-based urinary stones. Current treatment options are limited in their effectiveness at preventing stone recurrence and are often poorly tolerated. We report that the nutrition...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.4280
更新日期:2017-03-01 00:00:00
abstract::Because of their abundance, resistance to proteolysis, rapid aggregation and neurotoxicity, N-terminally truncated and, in particular, pyroglutamate (pE)-modified Abeta peptides have been suggested as being important in the initiation of pathological cascades resulting in the development of Alzheimer's disease. We fou...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.1872
更新日期:2008-10-01 00:00:00
abstract::We studied the effects of Lyn ablation on the survival of drug-resistant chronic myelogenous leukemia (CML) blast crisis cells using siRNA. Lyn siRNA reduced Lyn protein in both normal hematopoietic cells and BCR-ABL1-expressing (BCR-ABL1(+)) blasts by 80-95%. Within 48 h, siRNA-treated BCR-ABL1(+) blasts underwent ap...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1127
更新日期:2004-11-01 00:00:00
abstract::De novo mutations arising on the paternal chromosome make the largest known contribution to autism risk, and correlate with paternal age at the time of conception. The recurrence risk for autism spectrum disorders is substantial, leading many families to decline future pregnancies, but the potential impact of assessin...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-019-0711-0
更新日期:2020-01-01 00:00:00
abstract::Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) characterized by localized areas of demyelination. Although the etiology and pathogenesis of MS remain largely unknown, it is generally assumed that immune responses to myelin antigens contribute to the disease process. The exact se...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0198-078
更新日期:1998-01-01 00:00:00
abstract::Stimulating an immune response against cancer through adoptive transfer of tumor-targeting lymphocytes has shown great promise in hematological malignancies, but clinical efficacy against many common solid epithelial cancers remains low. Targeting 'neoantigens'-the somatic mutations expressed only by tumor cells-might...
journal_title:Nature medicine
pub_type: 杂志文章,评审
doi:10.1038/s41591-019-0596-y
更新日期:2019-10-01 00:00:00
abstract::Pulmonary hypertension (PH) is characterized by increased proliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs). Forkhead box O (FoxO) transcription factors are key regulators of cellular proliferation. Here we show that in pulmonary vessels and PASMCs of human and experimental PH lun...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3695
更新日期:2014-11-01 00:00:00
abstract:: ...
journal_title:Nature medicine
pub_type: 评论,杂志文章
doi:10.1038/s41591-018-0286-1
更新日期:2018-12-01 00:00:00
abstract::Overwhelming evidence that relationships between universities, physicians and the medical products industry benefit patients explains the ubiquitous calls to encourage such relationships. Yet accumulating 'conflict of interest' regulations in academic health centers, government and industry have had the opposite effec...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0411-437
更新日期:2011-04-01 00:00:00
abstract::Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that exhibits specific tumoricidal activity against a variety of tumors. It is expressed on different cells of the immune system and plays a role in natural killer cell-mediated tumor surveillance. In allogeneic he...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1202-797
更新日期:2002-12-01 00:00:00
abstract::Regulatory T cells (T(reg) cells) suppress autoreactive immune responses and limit the efficacy of tumor vaccines; however, it remains a challenge to selectively eliminate or inhibit T(reg) cells. In this study, the zinc-finger A20, a negative regulator of the Toll-like receptor and tumor necrosis factor receptor sign...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1721
更新日期:2008-03-01 00:00:00
abstract:: ...
journal_title:Nature medicine
pub_type: 评论,杂志文章
doi:10.1038/s41591-019-0362-1
更新日期:2019-02-01 00:00:00
abstract::Cytochrome P450 3A4 is an important mediator of drug catabolism that can be regulated by the steroid and xenobiotic receptor (SXR). We show here that SXR also regulates drug efflux by activating expression of the gene MDR1, which encodes the protein P-glycoprotein (ABCB1). Paclitaxel (Taxol), a commonly used chemother...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/87912
更新日期:2001-05-01 00:00:00
abstract::Deep brain stimulation (DBS) is a widely used neurosurgical approach to treating tremor and other movement disorders. In addition, the use of DBS in a number of psychiatric diseases, including obsessive-compulsive disorders and depression, is currently being tested. Despite the rapid increase in the number of individu...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1693
更新日期:2008-01-01 00:00:00
abstract::Programmed cell death (apoptosis) seems to be the principal mechanism whereby anti-oncogenic therapies such as chemotherapy and radiation effect their responses. Resistance to apoptosis, therefore, is probably a principal mechanism whereby tumors are able to overcome these cancer therapies. The transcription factor NF...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/7410
更新日期:1999-04-01 00:00:00
abstract::Misfolding of Cu/Zn-superoxide dismutase (SOD1) is emerging as a mechanism underlying motor neuron degeneration in individuals with amyotrophic lateral sclerosis (ALS) who carry a mutant SOD1 gene (SOD1 ALS). Here we describe a structure-guided approach to developing an antibody that specifically recognizes monomer-mi...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1559
更新日期:2007-06-01 00:00:00
abstract::The use of genetically manipulated mouse models, gene and protein discovery and the cataloguing of genetic mutations have each allowed us to obtain new insights into skeletal morphogenesis and remodeling. These techniques have made it possible to identify molecules that are obligatory for specific cellular functions, ...
journal_title:Nature medicine
pub_type: 杂志文章,评审
doi:10.1038/nm1593
更新日期:2007-07-01 00:00:00
abstract::Networks of interstitial cells of Cajal embedded in the musculature of the gastrointestinal tract are involved in the generation of electrical pacemaker activity for gastrointestinal motility. This pacemaker activity manifests itself as rhythmic slow waves in membrane potential, and controls the frequency and propagat...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0798-848
更新日期:1998-07-01 00:00:00
abstract::We formulate a two-phase paradigm of autoimmunity associated with systemic lupus erythematosus, the archetypal autoimmune disease. The initial Toll-like receptor (TLR)-independent phase is mediated by dendritic cell uptake of apoptotic cell debris and associated nucleic acids, whereas the subsequent TLR-dependent phas...
journal_title:Nature medicine
pub_type: 杂志文章,评审
doi:10.1038/nm1590
更新日期:2007-05-01 00:00:00
abstract::Physical function declines in old age, portending disability, increased health expenditures, and mortality. Cellular senescence, leading to tissue dysfunction, may contribute to these consequences of aging, but whether senescence can directly drive age-related pathology and be therapeutically targeted is still unclear...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-018-0092-9
更新日期:2018-08-01 00:00:00