Abstract:
:Comprehensively elucidating the molecular mechanisms of human immunodeficiency virus type 1 (HIV-1) latency is a priority to achieve a functional cure. As current 'shock' agents failed to efficiently reactivate the latent reservoir, it is important to discover new targets for developing more efficient latency-reversing agents (LRAs). Here, we found that TRIM28 potently suppresses HIV-1 expression by utilizing both SUMO E3 ligase activity and epigenetic adaptor function. Through global site-specific SUMO-MS study and serial SUMOylation assays, we identified that P-TEFb catalytic subunit CDK9 is significantly SUMOylated by TRIM28 with SUMO4. The Lys44, Lys56 and Lys68 residues on CDK9 are SUMOylated by TRIM28, which inhibits CDK9 kinase activity or prevents P-TEFb assembly by directly blocking the interaction between CDK9 and Cyclin T1, subsequently inhibits viral transcription and contributes to HIV-1 latency. The manipulation of TRIM28 and its consequent SUMOylation pathway could be the target for developing LRAs.
journal_name
Elifejournal_title
eLifeauthors
Ma X,Yang T,Luo Y,Wu L,Jiang Y,Song Z,Pan T,Liu B,Liu G,Liu J,Yu F,He Z,Zhang W,Yang J,Liang L,Guan Y,Zhang X,Li L,Cai W,Tang X,Gao S,Deng K,Zhang Hdoi
10.7554/eLife.42426subject
Has Abstractpub_date
2019-01-17 00:00:00issn
2050-084Xpii
42426journal_volume
8pub_type
杂志文章相关文献
eLife文献大全abstract::Human patients carrying PAPP-A2 inactivating mutations have low bone mineral density. The underlying mechanisms for this reduced calcification are poorly understood. Using a zebrafish model, we report that Papp-aa regulates bone calcification by promoting Ca2+-transporting epithelial cell (ionocyte) quiescence-prolife...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.52322
更新日期:2020-04-16 00:00:00
abstract::Candida albicans hyphae can reach enormous lengths, precluding their internalization by phagocytes. Nevertheless, macrophages engulf a portion of the hypha, generating incompletely sealed tubular phagosomes. These frustrated phagosomes are stabilized by a thick cuff of F-actin that polymerizes in response to non-canon...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.34798
更新日期:2018-03-19 00:00:00
abstract::Energy metabolism is essential for T cell function. However, how persistent antigenic stimulation affects T cell metabolism is unknown. Here, we report that long-term in vivo antigenic exposure induced a specific deficit in numerous metabolic enzymes. Accordingly, T cells exhibited low basal glycolytic flux and limite...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.30938
更新日期:2018-06-18 00:00:00
abstract::Coat protein complex II (COPII) mediates formation of the membrane vesicles that export newly synthesised proteins from the endoplasmic reticulum. The inner COPII proteins bind to cargo and membrane, linking them to the outer COPII components that form a cage around the vesicle. Regulated flexibility in coat architect...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.00951
更新日期:2013-09-17 00:00:00
abstract::Clinical trials are currently underway to assess the efficacy of forniceal deep brain stimulation (DBS) for improvement of memory in Alzheimer's patients, and forniceal DBS has been shown to improve learning and memory in a mouse model of Rett syndrome (RTT), an intellectual disability disorder caused by loss-of-funct...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.34031
更新日期:2018-03-23 00:00:00
abstract::To restore vision for the blind, several prosthetic approaches have been explored that convey raw images to the brain. So far, these schemes all suffer from a lack of bandwidth. An alternate approach would restore vision at the cognitive level, bypassing the need to convey sensory data. A wearable computer captures vi...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.37841
更新日期:2018-11-27 00:00:00
abstract::Mitochondria are dynamic organelles that must precisely control their protein composition according to cellular energy demand. Although nuclear-encoded mRNAs can be localized to the mitochondrial surface, the importance of this localization is unclear. As yeast switch to respiratory metabolism, there is an increase in...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.57814
更新日期:2020-08-07 00:00:00
abstract::Two-dimensional (2D) human skeletal muscle fiber cultures are ill-equipped to support the contractile properties of maturing muscle fibers. This limits their application to the study of adult human neuromuscular junction (NMJ) development, a process requiring maturation of muscle fibers in the presence of motor neuron...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.44530
更新日期:2019-05-14 00:00:00
abstract::Peptidoglycan (PG) is the main component of bacterial cell walls and the target for many antibiotics. PG biosynthesis is tightly coordinated with cell wall growth and turnover, and many of these control activities depend upon PASTA-domain containing eukaryotic-like serine/threonine protein kinases (PASTA-eSTK) that se...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.56048
更新日期:2020-05-29 00:00:00
abstract::The characteristics of goal-directed actions tend to resemble those of previously executed actions, but it is unclear whether such effects depend strictly on action history, or also reflect context-dependent processes related to predictive motor planning. Here we manipulated the time available to initiate movements af...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.26713
更新日期:2017-10-23 00:00:00
abstract::When a plant cell divides, four related proteins control the trafficking of vesicles and ensure that cargo that is normally recycled to the plasma membrane is instead re-routed to the plane of cell division. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.02747
更新日期:2014-04-08 00:00:00
abstract::Lamina-associated polypeptide 1 (LAP1) resides at the nuclear envelope and interacts with Torsins, poorly understood endoplasmic reticulum (ER)-localized AAA+ ATPases, through a conserved, perinuclear domain. We determined the crystal structure of the perinuclear domain of human LAP1. LAP1 possesses an atypical AAA+ f...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.03239
更新日期:2014-08-22 00:00:00
abstract::Aberrant expression of cancer genes and non-canonical RNA species is a hallmark of cancer. However, the mechanisms driving such atypical gene expression programs are incompletely understood. Here, our transcriptional profiling of a cohort of 50 primary clear cell renal cell carcinoma (ccRCC) samples from The Cancer Ge...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.09214
更新日期:2015-11-17 00:00:00
abstract::When a human catches a ball, they estimate future target location based on the current trajectory. How animals, small and large, encode such predictive processes at the single neuron level is unknown. Here we describe small target-selective neurons in predatory dragonflies that exhibit localized enhanced sensitivity f...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.26478
更新日期:2017-07-25 00:00:00
abstract::The choroid, which provides vascular supply to the outer retina, demonstrates progressive degeneration in aging and age-related macular degeneration (AMD). However mechanisms that maintain or compromise choroidal homeostasis are obscure. We discovered that the ablation of choroidal macrophages via CSF1R blockade was a...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.55564
更新日期:2020-04-01 00:00:00
abstract::AMPARs control fast synaptic communication between neurons and their function relies on auxiliary subunits, which importantly modulate channel properties. Although it has been suggested that AMPARs can bind to TARPs with variable stoichiometry, little is known about the effect that this stoichiometry exerts on certain...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.53946
更新日期:2020-05-26 00:00:00
abstract::Maintenance of transcription programs is challenged during mitosis when chromatin becomes condensed and transcription is silenced. How do the daughter cells re-establish the original transcription program? Here, we report that the TATA-binding protein (TBP), a key component of the core transcriptional machinery, remai...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.35621
更新日期:2018-06-25 00:00:00
abstract::Genome sequence data from a range of animal species are raising questions about the origins of glutamate receptors. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.43815
更新日期:2018-12-28 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving cytotoxic conformations of Cu, Zn superoxide dismutase (SOD1). A major challenge in understanding ALS disease pathology has been the identification and atomic-level characterization of these conformers. Here, we use a combination ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.07296
更新日期:2015-06-23 00:00:00
abstract::When a T cell and an antigen-presenting cell form an immunological synapse, rapid dynein-driven translocation of the centrosome toward the contact site leads to reorganization of microtubules and associated organelles. Currently, little is known about how the regulation of microtubule dynamics contributes to this proc...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.62876
更新日期:2020-12-21 00:00:00
abstract::Imaging sperm as they travel through the female reproductive tract has revealed new details about fertilization at the molecular level. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.64379
更新日期:2020-12-02 00:00:00
abstract::Dorsal/ventral (DV) patterning of the sea urchin embryo relies on a ventrally-localized organizer expressing Nodal, a pivotal regulator of the DV gene regulatory network. However, the inceptive mechanisms imposing the symmetry-breaking are incompletely understood. In Paracentrotus lividus, the Hbox12 homeodomain-conta...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.04664
更新日期:2014-12-02 00:00:00
abstract::Dietary restriction increases the longevity of many organisms, but the cell signaling and organellar mechanisms underlying this capability are unclear. We demonstrate that to permit long-term survival in response to sudden glucose depletion, yeast cells activate lipid-droplet (LD) consumption through micro-lipophagy (...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.21690
更新日期:2017-04-10 00:00:00
abstract::Trimethylamine-oxide (TMAO) is present in seafood which is considered to be beneficial for health. Deep-water animals accumulate TMAO to protect proteins, such as lactate dehydrogenase (LDH), against hydrostatic pressure stress (HPS). We hypothesized that TMAO exerts beneficial effects on the circulatory system and pr...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.57028
更新日期:2020-06-08 00:00:00
abstract::Social rank differentially influences how male and female mice respond to chronic stress. ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.63996
更新日期:2020-11-20 00:00:00
abstract::Appropriate generalization of learned responses to new situations is vital for adaptive behavior. We provide a circuit-level account of generalization in the electrosensory lobe (ELL) of weakly electric mormyrid fish. Much is already known in this system about a form of learning in which motor corollary discharge sign...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.44032
更新日期:2019-03-14 00:00:00
abstract::Orphans are genes restricted to a single phylogenetic lineage and emerge at high rates. While this predicts an accumulation of genes, the gene number has remained remarkably constant through evolution. This paradox has not yet been resolved. Because orphan genes have been mainly analyzed over long evolutionary time sc...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.01311
更新日期:2014-02-19 00:00:00
abstract::Two different cell signals often affect transcription of the same gene. In such cases, it is natural to ask how the combined transcriptional response compares to the individual responses. The most commonly used mechanistic models predict additive or multiplicative combined responses, but a systematic genome-wide evalu...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.59388
更新日期:2020-12-07 00:00:00
abstract::How mammalian tissues maintain their architecture and tissue-specificity is poorly understood. Previously, we documented both the indispensable role of the extracellular matrix (ECM) protein, laminin-111 (LN1), in the formation of normal breast acini, and the phenotypic reversion of cancer cells to acini-like structur...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.26148
更新日期:2018-03-21 00:00:00
abstract::During sleep, the brain experiences large fluctuations in blood volume and altered coupling between neural and vascular signals. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.64597
更新日期:2020-12-23 00:00:00