Abstract：
:Spatiotemporal protein reorganization at DNA damage sites induced by genotoxic chemotherapies is crucial for DNA damage response (DDR), which influences treatment response by directing cancer cell fate. This process is orchestrated by valosin-containing protein (VCP), an AAA+ ATPase that extracts polyubiquinated chromatin proteins and facilitates their turnover. However, because of the essential and pleiotropic effects of VCP in global proteostasis, it remains challenging practically to understand and target its DDR-specific functions. We describe a DNA-damage-induced phosphorylation event (Ser784), which selectively enhances chromatin-associated protein degradation mediated by VCP and is required for DNA repair, signaling, and cell survival. These functional effects of Ser784 phosphorylation on DDR correlate with a decrease in VCP association with chromatin, cofactors NPL4/UFD1, and polyubiquitinated substrates. Clinically, high phospho-Ser784-VCP levels are significantly associated with poor outcome among chemotherapy-treated breast cancer patients. Thus, Ser784 phosphorylation is a DDR-specific enhancer of VCP function and a potential predictive biomarker for chemotherapy treatments.
journal_name
Cell Repjournal_title
Cell reportsauthors
Zhu C,Rogers A,Asleh K,Won J,Gao D,Leung S,Li S,Vij KR,Zhu J,Held JM,You Z,Nielsen TO,Shao Jdoi
10.1016/j.celrep.2020.107745subject
Has Abstractpub_date
2020-06-09 00:00:00pages
107745issue
10issn
2211-1247pii
S2211-1247(20)30725-7journal_volume
31pub_type
杂志文章相关文献
Cell Reports文献大全abstract：:Stable unannotated transcripts (SUTs), some of which overlap protein-coding genes in antisense direction, are a class of non-coding RNAs. While case studies have reported important regulatory roles for several of such RNAs, their general impact on protein abundance regulation of the overlapping gene is not known. To t...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.05.043
更新日期：2016-06-21 00:00:00
abstract：:Electrons feed into the mitochondrial electron transport chain (mETC) from NAD- or FAD-dependent enzymes. A shift from glucose to fatty acids increases electron flux through FAD, which can saturate the oxidation capacity of the dedicated coenzyme Q (CoQ) pool and result in the generation of reactive oxygen species. To...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.03.009
更新日期：2016-04-05 00:00:00
abstract：:Tissue-resident memory T (TRM) cells provide key adaptive immune responses in infection, cancer, and autoimmunity. However, transcriptional heterogeneity of human intestinal TRM cells remains undefined. Here, we investigate transcriptional and functional heterogeneity of human TRM cells through study of donor-derived ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.108661
更新日期：2021-01-19 00:00:00
abstract：:Recent reports suggest that botulinum neurotoxin (BoNT) A, which is widely used clinically to inhibit neurotransmission, can spread within networks of neurons to have distal effects, but this remains controversial. Moreover, it is not known whether other members of this toxin family are transferred between neurons. He...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.06.104
更新日期：2016-08-16 00:00:00
abstract：:Cytotoxic CD8(+) T lymphocytes play a critical role in the host response to infection by viruses. The ability to secrete cytotoxic chemicals and cytokines is considered pivotal for eliminating virus. Of equal importance is how effector CD8(+) T cells home to virus-infected tissues. L-selectin has not been considered i...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.12.090
更新日期：2016-02-02 00:00:00
abstract：:Cell polarity arises through the spatial segregation of polarity regulators. PAR proteins are polarity regulators that localize asymmetrically to two opposing cortical domains. However, it is unclear how the spatially segregated PAR proteins interact to maintain their mutually exclusive partitioning. Here, single-mole...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.07.047
更新日期：2016-08-23 00:00:00
abstract：:Adipose tissue fibrosis development blocks adipocyte hypertrophy and favors ectopic lipid accumulation. Here, we show that adipose tissue fibrosis is associated with obesity and insulin resistance in humans and mice. Kinetic studies in C3H mice fed a high-fat diet show activation of macrophages and progression of fibr...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.03.062
更新日期：2014-05-22 00:00:00
abstract：:A mature olfactory sensory neuron (OSN) of the main olfactory epithelium (MOE) typically expresses one allele of one odorant receptor (OR) gene. It is widely thought that the great majority of the 1,141 intact mouse OR genes are expressed in one of four MOE zones (or bands or stripes), which are largely non-overlappin...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.02.110
更新日期：2020-03-24 00:00:00
abstract：:The distinct lineage potential is a key feature of hematopoietic stem cell (HSC) heterogeneity, but a subset of HSCs specialized for a single lymphoid compartment has not been identified. Here we report that HSCs expressing junctional adhesion molecule 2 (Jam2) at a higher level (Jam2high HSCs) have a greater T cell r...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.05.028
更新日期：2019-06-04 00:00:00
abstract：:In mammals, a cell's decision to divide is thought to be under the control of the Rb/E2F pathway. We previously found that inactivation of the Rb family of cell cycle inhibitors (Rb, p107, and p130) in quiescent liver progenitors leads to uncontrolled division and cancer initiation. Here, we show that, in contrast, de...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.06.025
更新日期：2014-07-24 00:00:00
abstract：:Mosquito-transmitted malaria parasites infect hepatocytes and asymptomatically replicate as liver stages. Using RNA sequencing, we show that a rodent malaria liver-stage infection stimulates a robust innate immune response including type I interferon (IFN) and IFNγ pathways. Liver-stage infection is suppressed by thes...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.03.018
更新日期：2014-04-24 00:00:00
abstract：:ASXL2 is an ETP family protein that interacts with PPARγ. We find that ASXL2-/- mice are insulin resistant, lipodystrophic, and fail to respond to a high-fat diet. Consistent with genetic variation at the ASXL2 locus and human bone mineral density, ASXL2-/- mice are also severely osteopetrotic because of failed osteoc...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.05.019
更新日期：2015-06-16 00:00:00
abstract：:The mechanisms dictating whether a cell proliferates or differentiates have undergone intense scrutiny, but they remain poorly understood. Here, we report that UPF1, a central component in the nonsense-mediated RNA decay (NMD) pathway, plays a key role in this decision by promoting the proliferative, undifferentiated ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.01.028
更新日期：2014-02-27 00:00:00
abstract：:Interleukin (IL)-17 signaling to the intestinal epithelium regulates the intestinal microbiome. Given the reported links between intestinal dysbiosis, bacterial translocation, and liver disease, we hypothesize that intestinal IL-17R signaling plays a critical role in mitigating hepatic inflammation. To test this, we s...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.10.042
更新日期：2019-11-19 00:00:00
abstract：:CRISPR genome engineering has become a powerful tool to functionally investigate the complex mechanisms of immune system regulation. While decades of work have aimed to genetically reprogram innate immunity, the utility of current approaches is restricted by poor knockout efficiencies or limited specificity for mature...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.107651
更新日期：2020-05-19 00:00:00
abstract：:Cancer cell-derived secretomes have been documented to play critical roles in cancer progression. Intriguingly, alternative extracellular roles of intracellular proteins are involved in various steps of tumor progression, which can offer strategies to fight cancer. Herein, we identify lung cancer progression-associate...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.01.037
更新日期：2020-02-11 00:00:00
abstract：:Cognitive capacities decline with age, an event accompanied by the altered transcription of synaptic plasticity genes. Here, we show that the transcriptional induction of Bdnf by a mnemonic stimulus is impaired in aged hippocampal neurons. Mechanistically, this defect is due to reduced NMDA receptor (NMDAR)-mediated a...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.08.028
更新日期：2016-09-13 00:00:00
abstract：:Within the field of computational neuroscience there are great expectations of finding new ways to rebalance the complex dynamic system of the human brain through controlled pharmacological or electromagnetic perturbation. Yet many obstacles remain between the ability to accurately predict how and where best to pertur...
journal_title：Cell reports
pub_type： 杂志文章,评审
doi：10.1016/j.celrep.2020.108128
更新日期：2020-09-08 00:00:00
abstract：:During cell division, the molecular motor Eg5 crosslinks overlapping antiparallel microtubules and pushes them apart to separate mitotic spindle poles. Dynein has been proposed as a direct antagonist of Eg5 at the spindle equator, pulling on antiparallel microtubules and favoring spindle collapse. Some of the experime...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2012.03.006
更新日期：2012-05-31 00:00:00
abstract：:Cyclin D1 encodes the regulatory subunit of a holoenzyme that phosphorylates RB and functions as a collaborative nuclear oncogene. The serine threonine kinase Akt plays a pivotal role in the control of cellular metabolism, survival, and mitogenic signaling. Herein, Akt1-mediated phosphorylation of downstream substrate...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.108151
更新日期：2020-09-15 00:00:00
abstract：:The number of essential telomerase components in the active ribonucleoprotein (RNP) has important implications for its mechanism of action yet is by and large unknown. We report that two differentially tagged TLC1 RNAs endogenously expressed in a heterozygous diploid and simultaneously detected via multi-color fluores...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.06.045
更新日期：2015-07-21 00:00:00
abstract：:Genetic and clinical association studies have identified disrupted in schizophrenia 1 (DISC1) as a candidate risk gene for major mental illness. DISC1 is interrupted by a balanced chr(1;11) translocation in a Scottish family in which the translocation predisposes to psychiatric disorders. We investigate the consequenc...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.07.061
更新日期：2015-09-01 00:00:00
abstract：:The amount and distribution of dystrophin protein in myofibers and muscle is highly variable in Becker muscular dystrophy and in exon-skipping trials for Duchenne muscular dystrophy. Here, we investigate a molecular basis for this variability. In muscle from Becker patients sharing the same exon 45-47 in-frame deletio...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.07.066
更新日期：2015-09-08 00:00:00
abstract：:Amyloidosis is a major problem in over one hundred diseases, including Alzheimer's disease (AD). Using the iDISCO visualization method involving targeted molecular labeling, tissue clearing, and light-sheet microscopy, we studied plaque formation in the intact AD mouse brain at up to 27 months of age. We visualized am...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.06.060
更新日期：2016-07-26 00:00:00
abstract：:NMDA receptors (NMDARs) are critical for physiological synaptic plasticity, learning, and memory and for pathological plasticity and neuronal death. The GluN1 subunit is encoded by a single gene, GRIN1, with 8 splice variants, but whether the diversity generated by this splicing has physiological consequences remains ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.11.087
更新日期：2019-12-24 00:00:00
abstract：:Hedgehog (Hh) signaling plays an integral role in vertebrate development, and its dysregulation has been accepted widely as a driver of numerous malignancies. While a variety of small molecules target Smoothened (Smo) as a strategy for Hh inhibition, Smo gain-of-function mutations have limited their clinical implement...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.03.001
更新日期：2015-04-07 00:00:00
abstract：:The Drosophila pharyngeal taste organs are poorly characterized despite their location at important sites for monitoring food quality. Functional analysis of pharyngeal neurons has been hindered by the paucity of molecular tools to manipulate them, as well as their relative inaccessibility for neurophysiological inves...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2017.11.041
更新日期：2017-12-05 00:00:00
abstract：:Memory B cells (MBCs) epitomize the adaptation of the immune system to the environment. We identify two MBC subsets in peripheral blood, CD27dull and CD27bright MBCs, whose frequency changes with age. Heavy chain variable region (VH) usage, somatic mutation frequency replacement-to-silent ratio, and CDR3 property chan...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.02.022
更新日期：2020-03-03 00:00:00
abstract：:Endosomal sorting complexes required for transport (ESCRT) drive cell surface receptor degradation resulting in attenuation of oncogenic signaling and pointing to a tumor suppressor function. Here, we show that loss of function of an ESCRT protein (HD-PTP encoded by the PTPN23 gene, located on the tumor suppressor gen...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.04.076
更新日期：2016-05-31 00:00:00
abstract：:Plasmodium parasites infect the liver and replicate inside hepatocytes before they invade erythrocytes and trigger clinical malaria. Analysis of host signaling pathways affected by liver-stage infection could provide critical insights into host-pathogen interactions and reveal targets for intervention. Using protein l...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2013.02.010
更新日期：2013-03-28 00:00:00
