Abstract：
:EGFR activates phosphatidylinositide 3-kinase (PI3K), but the mechanism underlying this activation is not completely understood. We demonstrated here that EGFR activation resulted in lysine acetyltransferase 5 (KAT5)-mediated K395 acetylation of the platelet isoform of phosphofructokinase 1 (PFKP) and subsequent translocation of PFKP to the plasma membrane, where the PFKP was phosphorylated at Y64 by EGFR. Phosphorylated PFKP binds to the N-terminal SH2 domain of p85α, which is distinct from binding of Gab1 to the C-terminal SH2 domain of p85α, and recruited p85α to the plasma membrane resulting in PI3K activation. PI3K-dependent AKT activation results in enhanced phosphofructokinase 2 (PFK2) phosphorylation and production of fructose-2,6-bisphosphate, which in turn promotes PFK1 activation. PFKP Y64 phosphorylation-enhanced PI3K/AKT-dependent PFK1 activation and GLUT1 expression promoted the Warburg effect, tumor cell proliferation, and brain tumorigenesis. These findings underscore the instrumental role of PFKP in PI3K activation and enhanced glycolysis through PI3K/AKT-dependent positive-feedback regulation.
journal_name
Mol Celljournal_title
Molecular cellauthors
Lee JH,Liu R,Li J,Wang Y,Tan L,Li XJ,Qian X,Zhang C,Xia Y,Xu D,Guo W,Ding Z,Du L,Zheng Y,Chen Q,Lorenzi PL,Mills GB,Jiang T,Lu Zdoi
10.1016/j.molcel.2018.03.018subject
Has Abstractpub_date
2018-04-19 00:00:00pages
197-210.e7issue
2eissn
1097-2765issn
1097-4164pii
S1097-2765(18)30221-1journal_volume
70pub_type
杂志文章相关文献
MOLECULAR CELL文献大全abstract：:Argonaute proteins are required for the biogenesis of some small RNAs (sRNAs), including the PIWI-interacting RNAs and some microRNAs. How Argonautes mediate maturation of sRNAs independent of their slicer activity is not clear. The maturation of the Neurospora microRNA-like sRNA, milR-1, requires the Argonaute protei...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2012.03.019
更新日期：2012-05-11 00:00:00
abstract：:In this issue of Molecular Cell, Dango and Mosammaparast discover that the human oxidative demethylase ALKBH3 functions in complex with a DNA helicase to eliminate N3-methylcytosine lesions from ssDNA and that specific cancer cell lines are dependent on this activity for proliferation (Dango et al., 2011). ...
journal_title：Molecular cell
pub_type： 评论,杂志文章
doi：10.1016/j.molcel.2011.10.009
更新日期：2011-11-04 00:00:00
abstract：:Poly(ADP-ribose) polymerase-1 (PARP-1) creates the posttranslational modification PAR from substrate NAD(+) to regulate multiple cellular processes. DNA breaks sharply elevate PARP-1 catalytic activity to mount a cell survival repair response, whereas persistent PARP-1 hyperactivation during severe genotoxic stress is...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2015.10.013
更新日期：2015-12-03 00:00:00
abstract：:HIV-1 Nef plays important roles in HIV-1 replication and pathogenesis. It is translated from completely spliced HIV-1 RNA, and its expression is inherently regulated at the levels of viral DNA transcription and RNA splicing. Here we show that Sam68 cytoplasmic mutants potently suppress Nef expression. The suppression ...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2008.11.024
更新日期：2009-01-16 00:00:00
abstract：:Many DNA viruses that are latent in dividing cells are noncovalent passengers on mitotic chromosomes and require specific viral-encoded and cellular factors for this activity. The chromosomal protein Brd4 is implicated in the hitchhiking of bovine papillomavirus-1 (BPV-1), and the viral protein E2 binds to both plasmi...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2006.11.002
更新日期：2006-12-28 00:00:00
abstract：:Among the five KCNQ channels, also known as the Kv7 voltage-gated potassium (Kv) channels, KCNQ2-KCNQ5 control neuronal excitability. Dysfunctions of KCNQ2-KCNQ5 are associated with neurological disorders such as epilepsy, deafness, and neuropathic pain. Here, we report the cryoelectron microscopy (cryo-EM) structures...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2020.10.037
更新日期：2021-01-07 00:00:00
abstract：:Dosage compensation in Drosophila is dependent on MSL proteins and involves hypertranscription of the male X chromosome, which ensures equal X-linked gene expression in both sexes. Here, we report the purification of enzymatically active MSL complexes from Drosophila embryos, Schneider cells, and human HeLa cells. We ...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2006.02.007
更新日期：2006-03-17 00:00:00
abstract：:Kong et al. (2020) present the low-resolution structure of the ATPɣS-bound human condensin I and II complexes and demonstrate that human condensins can extrude DNA loops in a symmetric and asymmetric fashion and compact nucleosome-bound DNA. ...
journal_title：Molecular cell
pub_type： 评论,杂志文章
doi：10.1016/j.molcel.2020.06.025
更新日期：2020-07-02 00:00:00
abstract：:The separation of sister chromatids in anaphase depends on the dissociation of cohesin from chromosomes. In vertebrates, some cohesin is removed from chromosomes at the onset of anaphase by proteolytic cleavage. In contrast, the bulk of cohesin is removed from chromosomes already in prophase and prometaphase by an unk...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(02)00473-2
更新日期：2002-03-01 00:00:00
abstract：:Study of mutant phenotypes is a fundamental method for understanding gene function. The construction of a near-complete collection of yeast knockouts (YKO) and the unique molecular barcodes (or TAGs) that identify each strain has enabled quantitative functional profiling of Saccharomyces cerevisiae. By using these TAG...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2004.09.035
更新日期：2004-11-05 00:00:00
abstract：:To determine whether replicational mutagenesis in the yeast genome is influenced by the positions of active origins, a reporter gene was placed in two orientations at multiple locations within a 39,000 bp region of chromosome III possessing two strong origins. The frequency of mutations resulting from misincorporation...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(02)00567-1
更新日期：2002-07-01 00:00:00
abstract：:Nucleosome loss from a promoter region has recently been described as a potential mechanism for transcriptional regulation. We investigated whether H3/H4 histone chaperones mediate the loss of nucleosomes from the promoter of the yeast PHO5 gene during transcriptional activation. We found that antisilencing function 1...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2004.05.016
更新日期：2004-06-04 00:00:00
abstract：:The presence of microbial or self DNA in the cytoplasm of mammalian cells is a danger signal detected by the DNA sensor cyclic-GMP-AMP (cGAMP) synthase (cGAS), which catalyzes the production of cGAMP that in turn serves as a second messenger to activate innate immune responses. Here we show that endogenous cGAMP in ma...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2013.05.022
更新日期：2013-07-25 00:00:00
abstract：:Ubiquitin-dependent proteolysis is an important mechanism that suppresses the beta-catenin transcription factor in cells without Wnt stimulation. A critical step in this regulatory pathway is to create a SCF(beta-TrCP) E3 ubiquitin ligase binding site for beta-catenin. Here we show that the SCF(beta-TrCP) binding site...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2008.10.023
更新日期：2008-12-05 00:00:00
abstract：:In this issue of Molecular Cell, Vonk et al. (2020) and Thiruvalluvan et al. (2020) identify key chaperones that confer resistance to protein aggregation in neural stem cells and become reduced upon differentiation. ...
journal_title：Molecular cell
pub_type： 评论,杂志文章
doi：10.1016/j.molcel.2020.03.028
更新日期：2020-04-16 00:00:00
abstract：:The diversity of mRNA lifetimes in bacterial cells is difficult to reconcile with the relaxed cleavage site specificity of RNase E, the endonuclease most important for governing mRNA degradation. This enzyme has generally been thought to locate cleavage sites by searching freely in three dimensions. However, our resul...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2019.01.044
更新日期：2019-04-18 00:00:00
abstract：:The mechanisms controlling growth and patterning along the proximal-distal axis of the vertebrate limb are yet to be understood. We show that restriction of expression of the homeobox gene Meis2 to proximal regions of the limb bud is essential for limb development, since ectopic Meis2 severely disrupts limb outgrowth....
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(00)80393-7
更新日期：1999-11-01 00:00:00
abstract：:MRE11 within the MRE11-RAD50-NBS1 (MRN) complex acts in DNA double-strand break repair (DSBR), detection, and signaling; yet, how its endo- and exonuclease activities regulate DSBR by nonhomologous end-joining (NHEJ) versus homologous recombination (HR) remains enigmatic. Here, we employed structure-based design with ...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2013.11.003
更新日期：2014-01-09 00:00:00
abstract：:Activating mutations in NOTCH1, an essential regulator of T cell development, are frequently found in human T cell acute lymphoblastic leukemia (T-ALL). Despite important advances in our understanding of Notch signal transduction, the regulation of Notch functions in the nucleus remains unclear. Using immunoaffinity p...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2012.08.022
更新日期：2012-11-09 00:00:00
abstract：:Mammalian target of rapamycin (mTOR) activity is regulated by assembly of two functionally distinct complexes, mTORC1 and mTORC2. In syndecan-4 (S4) null endothelial cells, mTORC2 activity is reduced, resulting in decreased Akt activation, while mTORC1 activity is increased. Levels of rictor, mLST8, and mSin-1 are unc...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2008.09.010
更新日期：2008-10-10 00:00:00
abstract：:Pilin assembly into type IV pili is required for virulence by bacterial pathogens that cause diseases such as cholera, pneumonia, gonorrhea, and meningitis. Crystal structures of soluble, N-terminally truncated pilin from Vibrio cholera toxin-coregulated pilus (TCP) and full-length PAK pilin from Pseudomonas aeruginos...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(03)00170-9
更新日期：2003-05-01 00:00:00
abstract：:While gapmers efficiently knock down as well as terminate transcription of nascent lncRNAs and mRNAs, Lee and Mendell (2020) and Lai et al. (2020) also demonstrate that Pol II termination is not observed with gapmers targeting the 3' terminal portions of the transcript. ...
journal_title：Molecular cell
pub_type： 评论,杂志文章
doi：10.1016/j.molcel.2020.02.010
更新日期：2020-03-05 00:00:00
abstract：:The liver plays a central role in the control of glucose homeostasis and is subject to complex regulation by substrates, insulin, and other hormones. To investigate the effect of the loss of direct insulin action in liver, we have used the Cre-loxP system to inactivate the insulin receptor gene in hepatocytes. Liver-s...
journal_title：Molecular cell
pub_type： 杂志文章
doi：
更新日期：2000-07-01 00:00:00
abstract：:Necroptosis is an important form of lytic cell death triggered by injury and infection, but whether mixed lineage kinase domain-like (MLKL) is sufficient to execute this pathway is unknown. In a genetic selection for human cell mutants defective for MLKL-dependent necroptosis, we identified mutations in IPMK and ITPK1...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2018.05.010
更新日期：2018-06-07 00:00:00
abstract：:In this issue of Molecular Cell, Lee et al. (2009) report that SUMOylation of nuclear receptors LXRalpha and LXRbeta plays a critical role in the transrepression of IFN-gamma-induced STAT1-dependent inflammatory responses in brain astrocytes. ...
journal_title：Molecular cell
pub_type： 评论,杂志文章
doi：10.1016/j.molcel.2009.09.002
更新日期：2009-09-24 00:00:00
abstract：:Heterochromatin is required to restrict aberrant expression of retrotransposons, but it remains poorly defined due to the underlying repeat-rich sequences. We dissected Suv39h-dependent histone H3 lysine 9 trimethylation (H3K9me3) by genome-wide ChIP sequencing in mouse embryonic stem cells (ESCs). Refined bioinformat...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2014.05.029
更新日期：2014-07-17 00:00:00
abstract：:Nonsense-mediated decay (NMD) degrades mRNAs containing a premature termination codon (PTC). PTCs are a frequent cause of human genetic diseases, and the NMD pathway is known to modulate disease severity. Since partial NMD attenuation can potentially enhance nonsense suppression therapies, better definition of human-s...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/j.molcel.2016.11.032
更新日期：2017-01-05 00:00:00
abstract：:APOBEC1 is the catalytic component of an RNA editing complex but shows homology to activation-induced cytidine deaminase (AID), a protein whose function is to potentiate diversification of immunoglobulin gene DNA. Here, we show that APOBEC1 and its homologs APOBEC3C and APOBEC3G exhibit potent DNA mutator activity in ...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(02)00742-6
更新日期：2002-11-01 00:00:00
abstract：:Nhp6A and Nhp6B are HMG1-like proteins required for the growth of S. cerevisiae at elevated temperatures. We show that the conditional lethality of an nhp6 strain results from defective transcription of SNR6 (U6 snRNA) by RNA polymerase III. Overexpression of U6 snRNA or Brf1, a limiting component of TFIIIB, and an ac...
journal_title：Molecular cell
pub_type： 杂志文章
doi：10.1016/s1097-2765(01)00179-4
更新日期：2001-02-01 00:00:00
abstract：:Heterochromatin is refractory to DNA transactions, including repair. In a recent issue of Molecular Cell, Goodarzi et al. (2008) reveal how the central transducing kinase of the DNA damage response relieves this natural barrier by increasing heterochromatic DNA accessibility. ...
journal_title：Molecular cell
pub_type： 评论,杂志文章
doi：10.1016/j.molcel.2008.07.004
更新日期：2008-08-08 00:00:00
