Product References
Katanin Grips the β-Tubulin Tail through an Electropositive Double Spiral to Sever Microtubules.
Developmental cell
Zehr EA,Szyk A,Szczesna E,Roll-Mecak A
The AAA ATPase katanin severs microtubules. It is critical in cell division, centriole biogenesis, and neuronal morphogenesis. Its mutation causes microcephaly. The microtubule templates katanin hexamerization and activates its ATPase. The structural basis for these activities and how they lead to severing is unknown. Here, we show that β-tubulin tails are necessary and sufficient for severing. Cryoelectron microscopy (cryo-EM) structures reveal the essential tubulin tail glutamates gripped
Mon Jan 06 00:00:00 UTC 2020
Ddx56 maintains proliferation of mouse embryonic stem cells via ribosome assembly and interaction with the Oct4/Sox2 complex.
Stem cell research & therapy
Wang J,Liu J,Ye M,Liu F,Wu S,Huang J,Shi G
Thu Jul 23 00:00:00 UTC 2020
Correction: TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition.
The Journal of biological chemistry
Zhang H,Liu CY,Zha ZY,Zhao B,Yao J,Zhao S,Xiong Y,Lei QY,Guan KL
Fri Apr 12 00:00:00 UTC 2019
Src kinase phosphorylates Notch1 to inhibit MAML binding.
Scientific reports
LaFoya B,Munroe JA,Pu X,Albig AR
Notch signaling is a form of intercellular communication which plays pivotal roles at various stages in development and disease. Previous findings have hinted that integrins and extracellular matrix may regulate Notch signaling although a mechanistic basis for this interaction had not been identified. Here we reveal that the regulation of Notch by integrins and extracellular matrix is carried out by Src family kinases (SFKs) working downstream of integrins. We identify a physical interaction bet
Fri Oct 19 00:00:00 UTC 2018
Existing drugs as broad-spectrum and potent inhibitors for Zika virus by targeting NS2B-NS3 interaction.
Cell research
Li Z,Brecher M,Deng YQ,Zhang J,Sakamuru S,Liu B,Huang R,Koetzner CA,Allen CA,Jones SA,Chen H,Zhang NN,Tian M,Gao F,Lin Q,Banavali N,Zhou J,Boles N,Xia M,Kramer LD,Qin CF,Li H
Recent outbreaks of Zika virus (ZIKV) highlight an urgent need for therapeutics. The protease complex NS2B-NS3 plays essential roles during flaviviral polyprotein processing and thus represents an attractive drug target. Here we developed a split luciferase complementation-based high-throughput screening assay to identify orthosteric inhibitors that directly target flavivirus NS2B-NS3 interactions. By screening a total of 2 816 approved and investigational drugs we identified three potent candid
Tue Aug 01 00:00:00 UTC 2017
Reactive oxygen species trigger Parkin/PINK1 pathway-dependent mitophagy by inducing mitochondrial recruitment of Parkin.
The Journal of biological chemistry
Xiao B,Goh JY,Xiao L,Xian H,Lim KL,Liou YC
Defective mitophagy linked to dysfunction in the proteins Parkin and PTEN-induced putative kinase 1 (PINK1) is implicated in the pathogenesis of Parkinson's disease. Although the mechanism by which Parkin mediates mitophagy in a PINK1-dependent manner is becoming clearer, the triggers for this mitophagy pathway remain elusive. Reactive oxygen species (ROS) have been suggested as such triggers, but this proposal remains controversial because ROS scavengers fail to retard mitophagy. Here we demons
Fri Oct 06 00:00:00 UTC 2017
Protein substrates of the arginine methyltransferase Hmt1 identified by proteome arrays.
Proteomics
Low JK,Im H,Erce MA,Hart-Smith G,Snyder MP,Wilkins MR
Arginine methylation on nonhistone proteins is associated with a number of cellular processes including RNA splicing, protein localization, and the formation of protein complexes. In this manuscript, Saccharomyces cerevisiae proteome arrays carrying 4228 proteins were used with an antimethylarginine antibody to first identify 88 putatively arginine-methylated proteins. By treating the arrays with recombinant arginine methyltransferase Hmt1, 42 proteins were found to be possible substrates of thi
Mon Feb 01 00:00:00 UTC 2016
FAM83H and casein kinase I regulate the organization of the keratin cytoskeleton and formation of desmosomes.
Scientific reports
Kuga T,Sasaki M,Mikami T,Miake Y,Adachi J,Shimizu M,Saito Y,Koura M,Takeda Y,Matsuda J,Tomonaga T,Nakayama Y
Wed May 25 00:00:00 UTC 2016
Characterizing Requirements for Small Ubiquitin-like Modifier (SUMO) Modification and Binding on Base Excision Repair Activity of Thymine-DNA Glycosylase in Vivo.
The Journal of biological chemistry
McLaughlin D,Coey CT,Yang WC,Drohat AC,Matunis MJ
Thymine-DNA glycosylase (TDG) plays critical roles in DNA base excision repair and DNA demethylation. It has been proposed, based on structural studies and in vitro biochemistry, that sumoylation is required for efficient TDG enzymatic turnover following base excision. However, whether sumoylation is required for TDG activity in vivo has not previously been tested. We have developed an in vivo assay for TDG activity that takes advantage of its recently discovered role in DNA demethylation and se
Fri Apr 22 00:00:00 UTC 2016
Glyceraldehyde-3-phosphate dehydrogenase is activated by lysine 254 acetylation in response to glucose signal.
The Journal of biological chemistry
Li T,Liu M,Feng X,Wang Z,Das I,Xu Y,Zhou X,Sun Y,Guan KL,Xiong Y,Lei QY
The altered metabolism in most tumor cells consists of elevated glucose uptake and increased glycolysis even in the presence of high oxygen tension. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an obligatory enzyme in glycolysis. Here we report that acetylation at lysine 254 (K254) increases GAPDH activity in response to glucose. Furthermore acetylation of GAPDH (K254) is reversibly regulated by the acetyltransferase PCAF and the deacetylase HDAC5. Substitution of K254 to glutamine compro
Fri Feb 07 00:00:00 UTC 2014
Targeted polyubiquitylation of RASSF1C by the Mule and SCFβ-TrCP ligases in response to DNA damage.
The Biochemical journal
Zhou X,Li TT,Feng X,Hsiang E,Xiong Y,Guan KL,Lei QY
RASSF1A [Ras association (RalGDS/AF-6) domain family member 1A] and RASSF1C are two ubiquitously expressed isoforms of the RASSF1 gene. The promoter of RASSF1A is frequently hypermethylated, resulting in inactivation in various human cancers. RASSF1A is implicated in the regulation of apoptosis, microtubule stability and cell cycle arrest. However, little is known about the regulation and function of RASSF1C. In the present study we show that exogenously expressed RASSF1C is a very unstable prot
Sun Jan 01 00:00:00 UTC 2012
The N-terminal phosphodegron targets TAZ/WWTR1 protein for SCFβ-TrCP-dependent degradation in response to phosphatidylinositol 3-kinase inhibition.
The Journal of biological chemistry
Huang W,Lv X,Liu C,Zha Z,Zhang H,Jiang Y,Xiong Y,Lei QY,Guan KL
The Hippo tumor suppressor pathway plays a major role in development and organ size control, and its dysregulation contributes to tumorigenesis. TAZ (transcriptional co-activator with PDZ-binding motif; also known as WWTR1) is a transcription co-activator acting downstream of the Hippo pathway, and increased TAZ protein levels have been associated with human cancers, such as breast cancer. Previous studies have shown that TAZ is inhibited by large tumor suppressor (LATS)-dependent phosphorylatio
Fri Jul 27 00:00:00 UTC 2012
PP1 cooperates with ASPP2 to dephosphorylate and activate TAZ.
The Journal of biological chemistry
Liu CY,Lv X,Li T,Xu Y,Zhou X,Zhao S,Xiong Y,Lei QY,Guan KL
The Hippo pathway regulates organ size by controlling both cell proliferation and apoptosis. TAZ functions as a transcriptional co-activator downstream of the Hippo pathway and has been implicated in human cancer development. A key step in the Hippo-TAZ pathway is phosphorylation of TAZ by LATS kinase, which leads to TAZ inhibition by both cytoplasmic retention and degradation. However, the mechanism of TAZ dephosphorylation and the responsible phosphatase are unknown. Here, we identified PP1 as
Fri Feb 18 00:00:00 UTC 2011
The hippo tumor pathway promotes TAZ degradation by phosphorylating a phosphodegron and recruiting the SCF{beta}-TrCP E3 ligase.
The Journal of biological chemistry
Liu CY,Zha ZY,Zhou X,Zhang H,Huang W,Zhao D,Li T,Chan SW,Lim CJ,Hong W,Zhao S,Xiong Y,Lei QY,Guan KL
The TAZ transcription co-activator promotes cell proliferation and epithelial-mesenchymal transition. TAZ is inhibited by the Hippo tumor suppressor pathway, which promotes TAZ cytoplasmic localization by phosphorylation. We report here that TAZ protein stability is controlled by a phosphodegron recognized by the F-box protein β-TrCP and ubiquitylated by the SCF/CRL1(β-TrCP) E3 ligase. The interaction between TAZ and β-TrCP is regulated by the Hippo pathway. Phosphorylation of a p
Fri Nov 26 00:00:00 UTC 2010
TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition.
The Journal of biological chemistry
Zhang H,Liu CY,Zha ZY,Zhao B,Yao J,Zhao S,Xiong Y,Lei QY,Guan KL
The TAZ transcription co-activator has been shown to promote cell proliferation and to induce epithelial-mesenchymal transition. Recently we have demonstrated that TAZ is phosphorylated and inhibited by the Hippo tumor suppressor pathway, which is altered in human cancer. The mechanism of TAZ-mediated transcription is unclear. We demonstrate here that TEAD is a key downstream transcription factor mediating the function of TAZ. Disruption of TEAD-TAZ binding or silencing of TEAD expression blocke
Fri May 15 00:00:00 UTC 2009
TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the hippo pathway.
Molecular and cellular biology
Lei QY,Zhang H,Zhao B,Zha ZY,Bai F,Pei XH,Zhao S,Xiong Y,Guan KL
TAZ is a WW domain containing a transcription coactivator that modulates mesenchymal differentiation and development of multiple organs. In this study, we show that TAZ is phosphorylated by the Lats tumor suppressor kinase, a key component of the Hippo pathway, whose alterations result in organ and tissue hypertrophy in Drosophila and contribute to tumorigenesis in humans. Lats phosphorylates TAZ on several serine residues in the conserved HXRXXS motif and creates 14-3-3 binding sites, leading t
Tue Apr 01 00:00:00 UTC 2008
