CSTP1, a Novel Protein Phosphatase, Blocks Cell Cycle, Promotes Cell Apoptosis, and Suppresses Tumor Growth of Bladder Cancer by Directly Dephosphorylating Akt at Ser473 Site

Zhuo, Dexiang; Zhang, Xiaowei; Jin, Bo; Zhang, Zheng; Xie, Bu‐Shan; Wu, Chenglin; Gong, Kan; Mao, Zebin

doi:10.1371/journal.pone.0065679

Cited by 24 publications

(53 citation statements)

References 37 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Abnormalities in apoptosis and cell EMT changes have been closely correlated with bladder cancer progression [21]. Various treatment agents often inhibit tumour cells by promoting apoptosis, blocking cell cycle arrest or inhibiting cell EMT changes [22,23]. In this study, we found that a new Akt inhibitory agent, CTT, induced significant decreases in cell proliferation and suppressed the migration and invasion of bladder cells.…”

Section: Discussionmentioning

confidence: 68%

Cryptotanshinone Inhibites Bladder Cancer Cell Proliferation and Promotes Apoptosis via the PTEN/PI3K/AKT Pathway

Liu¹,

Lin²,

Chen³

et al. 2020

J. Cancer

View full text Add to dashboard Cite

Cryptotanshinone (CTT), extracted from the root of Salvia miltiorrhiza Bunge (Danshen), exhibits activities against a variety of human cancers in vitro and in vivo. The purpose of this study was to investigate the potential inhibitory effect of CTT on bladder cancer. In this study, we found that CTT inhibited bladder cancer cell proliferation, migration, and invasion and promoted apoptosis. In addition, CTT modulated the expression of proteins via the PI3K/AKT pathway, and the inhibition of PI3K/AKT signalling was due to induction of PTEN expression. Taken together, the results of the present study demonstrated the anticancer effect of CTT on bladder cancer cells, which might be associated with the downregulation of PI3K/AKT/mTOR and NF-κB signalling pathway proteins, and this inhibition was mediated by the induction of PTEN.

show abstract

Section: Discussionmentioning

confidence: 68%

Cryptotanshinone Inhibites Bladder Cancer Cell Proliferation and Promotes Apoptosis via the PTEN/PI3K/AKT Pathway

Liu¹,

Lin²,

Chen³

et al. 2020

J. Cancer

View full text Add to dashboard Cite

show abstract

“…One of our identified proteins was the recently characterized CPPED1 [19,41]. Additionally, we detected a genetic association between the length of term pregnancy and CPPED1 but not for any other genes encoding detected proteins.…”

Section: Discussionmentioning

confidence: 68%

“…Zhuo et al [19] detected decreased levels of CPPED1 mRNA in bladder cancer but not in pancreatic, liver, stomach, colon or renal cancer. They also found that CPPED1 has serine/threonine-protein phosphatase activity and can inactivate AKT1 through specific dephosphorylation of Ser473.…”

Section: Discussionmentioning

confidence: 99%

Expression of CPPED1 in human trophoblasts is associated with timing of term birth

Haapalainen

Karjalainen

Daddali

et al. 2017

J Cellular Molecular Medi

View full text Add to dashboard Cite

Understanding of timing of human parturition is incomplete. Therefore, we carried out proteomic analyses of full‐term placentas from uncomplicated pregnancies to identify protein signatures associated with the onset of spontaneous delivery. We found quantitative associations of 10 proteins with spontaneous term birth, evident either in the basal or in the chorionic plates or in both. Additional 18 proteins were associated according to the location within placenta indicating local variations in protein amounts. Calcineurin‐like phosphoesterase domain‐containing 1 (CPPED1), a phosphatase previously suggested dephosphorylating AKT1/PKB, was one of the identified proteins. qRT‐PCR revealed the mRNA level of CPPED1 was higher in elective caesarean deliveries than in spontaneous births, while immunohistochemistry showed CPPED1 in cytotrophoblasts, syncytiotrophoblasts and extravillous trophoblasts. Noteworthy, phosphorylation status of AKT1 did not differ between placentas from elective caesarean and spontaneous deliveries. Additionally, analyses of samples from infants indicated that single‐nucleotide polymorphisms rs11643593 and rs8048866 of CPPED1 were associated with duration of term pregnancy. Finally, post‐transcriptional silencing of CPPED1 in cultured HTR8/SVneo cells by siRNAs affected gene expression in pathways associated with inflammation and blood vessel development. We postulate that functions regulated by CPPED1 in trophoblasts at choriodecidual interphase have a role in the induction of term labour, but it may be independent of AKT1.

show abstract

“…CPPED1 (also known as CSPT1) is a serine/threonine phosphatase that specifically dephosphorylates AKT. 35 ADO is a thiol dioxygenase that catalyzes the oxidation of cysteamine to hypotaurine. 36 Neither have been previously reported as a target of SAHA, 12,14,37,38 nor do they exhibit sequence similarities with HDACs.…”

Section: Acs Chemical Biologymentioning

confidence: 99%

Deciphering the Cellular Targets of Bioactive Compounds Using a Chloroalkane Capture Tag

et al. 2015

View full text Add to dashboard Cite

Phenotypic screening of compound libraries is a significant trend in drug discovery, yet success can be hindered by difficulties in identifying the underlying cellular targets. Current approaches rely on tethering bioactive compounds to a capture tag or surface to allow selective enrichment of interacting proteins for subsequent identification by mass spectrometry. Such methods are often constrained by ineffective capture of low affinity and low abundance targets. In addition, these methods are often not compatible with living cells and therefore cannot be used to verify the pharmacological activity of the tethered compounds. We have developed a novel chloroalkane capture tag that minimally affects compound potency in cultured cells, allowing binding interactions with the targets to occur under conditions relevant to the desired cellular phenotype. Subsequent isolation of the interacting targets is achieved through rapid lysis and capture onto immobilized HaloTag protein. Exchanging the chloroalkane tag for a fluorophore, the putative targets identified by mass spectrometry can be verified for direct binding to the compound through resonance energy transfer. Using the interaction between histone deacetylases (HDACs) and the inhibitor, Vorinostat (SAHA), as a model system, we were able to identify and verify all the known HDAC targets of SAHA as well as two previously undescribed targets, ADO and CPPED1. The discovery of ADO as a target may provide mechanistic insight into a reported connection between SAHA and Huntington's disease.

show abstract

CSTP1, a Novel Protein Phosphatase, Blocks Cell Cycle, Promotes Cell Apoptosis, and Suppresses Tumor Growth of Bladder Cancer by Directly Dephosphorylating Akt at Ser473 Site

Cited by 24 publications

References 37 publications

Cryptotanshinone Inhibites Bladder Cancer Cell Proliferation and Promotes Apoptosis via the PTEN/PI3K/AKT Pathway

Cryptotanshinone Inhibites Bladder Cancer Cell Proliferation and Promotes Apoptosis via the PTEN/PI3K/AKT Pathway

Expression of CPPED1 in human trophoblasts is associated with timing of term birth

Deciphering the Cellular Targets of Bioactive Compounds Using a Chloroalkane Capture Tag

Contact Info

Product

Resources

About