• We present evidence that the cyclin-dependent kinase inhibitor p27 Kip1 , is phosphorylated at Thr 198 downstream of the Peutz-Jeghers syndrome protein-AMP-activated protein kinase (LKB1-AMPK) energy-sensing pathway, thereby increasing p27 stability and directly linking sensing of nutrient concentration and bioenergetics to cell-cycle progression. (elsevierpure.com)
  • The cyclin-dependent kinase (CDK) inhibitor p27(Kip1) is a key cell-cycle regulator of G1-to-S phase transition [ 1 ]. (biomedcentral.com)
  • Phospho-p27 Kip1 (Thr198) Antibody detects endogenous levels of p27 Kip1 only when phosphorylated at Threonine 198. (affbiotech.cn)
  • p27 expression is reduced in pancreatic adenocarcinomas and decreased protein levels of p27 may play a role in the differentiation of pancreatic cancer. (biomedcentral.com)
  • This apparent increase in p27 protein expression might have been due to either increased synthesis or decreased degradation, or a combination of both [ 1 ]. (biomedcentral.com)
  • Taken together, our data suggest that magnolol at a higher concentration of 100 μM induced apopotosis in U373 cells through cSrc-mediated upregulation of p27/Kip1. (tmu.edu.tw)
  • In this study, we report that cell cycle entry proceeded normally in HSCs null for cyclin-dependent kinase (CDK) inhibitor p57 due to compensatory upregulation of p27. (elsevierpure.com)
  • The CDKN1B gene provides instructions for making a protein called p27. (medlineplus.gov)
  • Most of the CDKN1B gene mutations that cause multiple endocrine neoplasia type 4 change single protein building blocks (amino acids) in the p27 protein. (medlineplus.gov)
  • Mice lacking the tumor suppressors p16(Ink4a) (Cdkn2a, cyclin-dependent kinase inhibitor 2a), p19(Arf) (an alternative reading frame product of Cdkn2a,), and p27(Kip1) (Cdkn1b, cyclin-dependent kinase inhibitor 1b) result in malignant progression of epithelial cancers, sarcomas, and melanomas, respectively. (koreamed.org)
  • Magnolol at a higher concentration of 100 μM, however, induced apoptosis and upregulated p27/Kip1 expression in U373. (tmu.edu.tw)
  • In the present study, we further studied whether the increased p27/Kip1 expression contributes to the magnolol-induced apoptosis in U373. (tmu.edu.tw)
  • Our data show that knock-down of p27/Kip1 expression significantly suppressed the magnolol-induced apoptosis, suggesting that p27/Kip1 might play an important role in the regulation of magnolol-induced apoptosis. (tmu.edu.tw)
  • To delineate the possible signaling pathways involved in the magnolol-induced increases of p27/Kip1 expression and apoptosis, we found that magnolol (100 μM) increased the levels of phosphorylated cSrc (p-cSrc), p-ERK, p-p38 MAP kinase (p-p38 MAPK), and p-AKT but not p-JNK in U373. (tmu.edu.tw)
  • Moreover, pretreatment of U373 with a cSrc inhibitor (PP2), a PI3K inhibitor (LY294002), an ERK inhibitor (PD98059), or a p38 MAPK inhibitor (SB203580) but not a JNK inhibitor (SP600125) significantly reduced the magnolol-induced increases of p27/Kip1 protein levels and apoptosis. (tmu.edu.tw)
  • Chen, LC & Lee, WS 2013, ' P27/Kip1 is responsible for magnolol-induced U373 apoptosis in vitro and in Vivo ', Journal of Agricultural and Food Chemistry , vol. 61, no. 11, pp. 2811-2819. (tmu.edu.tw)
  • Under stress conditions that activate the LKB1-AMPK pathway with subsequent induction of autophagy, p27 knockdown results in apoptosis. (elsevierpure.com)
  • Treatment of WEHI-231 cells with Ig-specific antisera leads to growth arrest in the late G 1 phase of cell cycle concomitant with NF-κB inactivation, NF-κB-mediated c-Myc down-regulation, p27 Kip1 up-regulation, and apoptosis ( 1 , 2 , 5 , 6 ). (aai.org)
  • Particular emphasis was placed on the roles of growth arrest and c-Myc, p27 Kip1 , and p21 WAF1 expression, because all of these elements contribute to clonal deletion. (aai.org)
  • Finally, in contrast to clonal deletion, PAH-induced pro/pre-B cell death was not dependent on p27 Kip1 or p21 WAF1 up-regulation but did coincide with p53 induction. (aai.org)
  • Up-regulation appears to be specific to p27 because expression of cyclin D1, E, and A, and p21Cip1/Waf1 was not modulated by these agents. (biomedcentral.com)
  • p27Kip1 is a candidate tumor suppressor gene. (neobiotechnologies.com)
  • Patients and Methods: For analysis of p27 Kip1 expression in 420 tumor nephrectomy specimens obtained from 420 consecutively included patients, tissue microarrays were used comprising 1260 tissue samples each obtained from the tumor itself, the invasive front as well as the non-malignant surrounding parenchyma. (uni-luebeck.de)
  • Based on this function, p27 is described as a tumor suppressor protein. (medlineplus.gov)
  • Cells with a shortage of functional p27 can divide too quickly or in an uncontrolled way, forming a tumor. (medlineplus.gov)
  • The p27 Kip1 induction appears to be a direct consequence of the loss of transcriptional repression mediated by c-Myc ( 7 ). (aai.org)
  • Additionally, the use of simvastatin plus classII histone deacetylase (HDAC) inhibitor (MC1568) induced further overexpression of p27(KIP1) by inhibiting HDAC5 induction originated from downregulated EZH2 in CRC cells and synergistically led to considerable antiproliferative effects. (nih.gov)
  • SDS-PAGE Analysis Purified p27 Mouse Monoclonal Antibody (KIP1/1357). (neobiotechnologies.com)
  • In Western blotting of cell lysates from 7 human breast cancer cell lines (ZR75-1, ZR75-30, MCF-7, MDAMB453, T47D, CAL51, 734B), the antibody labels a single band corresponding to p27Kip1. (neobiotechnologies.com)
  • Regulation can occur through modification of the p27 protein's structure, its interaction with other proteins, or its localization within the cell. (medlineplus.gov)
  • We found that heat shock cognate protein 70 (Hsc70) interacts with both p57 and p27 and that the subcellular localization of Hsc70 was critical to maintain HSC cell cycle kinetics. (elsevierpure.com)
  • Taken together, these data suggest that regulation of cytoplasmic localization of Hsc70/cyclin D1 complex by p57 and p27 is a key intracellular mechanism in controlling HSC dormancy. (elsevierpure.com)
  • Transcriptional and translational control, sequestration in cyclin D1 complexes and localization all regulate p27 in G1 phase. (biomedcentral.com)
  • Strong nuclear staining using KIP1/1357 at 2ug/ml in PBS for 30min RT. (neobiotechnologies.com)
  • Combined deficiency of p57 and p27 in HSCs resulted in nuclear import of an Hsc70/cyclin D1 complex, concomitant with Rb phosphorylation, and elicited severe defects in maintaining HSC quiescence. (elsevierpure.com)
  • CRM1/Ran-mediated nuclear export of p27(Kip1) involves a nuclear export signal and links p27 export and proteolysis. (mpg.de)
  • The purpose of our study was to investigate the immunohistochemical expression of TGF-β1 and p27 in pancreatic adenocarcinomas and to compare the findings with the clinicopathological features and survival. (biomedcentral.com)
  • We also aimed to evaluate the expression of TGF-β1 and p27 in the context of other cell cycle and proliferation markers such as cyclin D1 and Ki-67. (biomedcentral.com)
  • We examined TGF-β1 and p27 expression immunohistochemically in 63 cases of invasive ductal adenocarcinoma of the pancreas. (biomedcentral.com)
  • In the univariate analysis, neither TGF-β1 nor p27 expression was related with patient survival. (biomedcentral.com)
  • It has also been demonstrated that TGF-β induced cell cycle arrest can be partially attributed to the regulatory effects of TGF-β on both the expression and activity of cyclin-dependent kinase inhibitors [CDKI] such as p21 and p27. (biomedcentral.com)
  • Background: The expression of the negative cell cycle regulator p27 Kip1 is frequently found to be deregulated in various human cancer types. (uni-luebeck.de)
  • Whether the expression of p27 Kip1 can be used as a prognostic marker for renal cell cancer patients still remains to be clarified. (uni-luebeck.de)
  • Results: In univariate survival analysis, decreased expression of p27 Kip1 within tissue cores obtained from the invasion front was significantly correlated with the patients' disease-specific long-term survival (p=0.02, log rank test). (uni-luebeck.de)
  • In contrast, expression of p27 Kip1 within the primary tumors was not identified to reveal any prognostically important information. (uni-luebeck.de)
  • 0.01) as well as decreased expression of p27 Kip1 (p=0.04) within the invasion front tissue samples independently predicted the disease-specific long-term survival following surgery. (uni-luebeck.de)
  • Ectopic expression of wild-type and phosphomimetic Thr 198 to Asp 198 (T198D), but not unstable Thr 198 to Ala 198 (p27 T198A ) is sufficient to induce autophagy. (elsevierpure.com)
  • This report addresses the question of whether various nutritional and chemopreventive anti-cancer agents up-regulate the expression of p27 in preneoplastic and neoplastic cells. (biomedcentral.com)
  • Experimental evidence presented in the first half of this report shows that these agents fairly faithfully up-regulate expression of p27 in mouse epidermal (JB6) and human breast cancer (MCF7, MDA-MB-321, and AU565) cells. (biomedcentral.com)
  • Up-regulation of the expression of p27 is likely due to the activation of translation rather than transcription of p27 because (a) up-regulation is mediated by the 5'-untranslated region (-575) of the p27 gene and (b) the antibiotic actinomycin D, an inhibitor of transcription, did not attenuate the up-regulation of p27. (biomedcentral.com)
  • Amino acid deficiencies also up-regulate the expression of p27 using some components of this pathway. (biomedcentral.com)
  • b) 4-Hydroxytamoxifen (but not tamoxifen), genistein (but not genistin), daidzein, and probably other nutritional and chemopreventive anti-cancer agents could up-regulate expression of p27 via receptor protein tyrosine kinases (RPTKs), phosphoinositide 3-kinase (PI3K), phosphoinosite-dependent kinase (PDK), Akt/PKB and mTOR. (biomedcentral.com)
  • c) Expression of p27 could also be up-regulated via RPTKs followed by MAPKs - MEK, ERK and p38MAPK - and probably MNK. (biomedcentral.com)
  • Finally, (d) global hypomethylation of 5'-m 7 G cap of mRNAs could also up-regulate expression of p27. (biomedcentral.com)
  • Based on these findings, we conclude that various nutritional and chemopreventive anti-cancer agents up-regulate expression of p27 in (pre)neoplastic cells. (biomedcentral.com)
  • Preliminary studies using either N -methyl- N -nitrosourea (MNU)-induced rat breast cancer model or human breast cancer cell lines in vitro had suggested, but not proved, that nutritional and chemopreventive anti-cancer agents increase p27 protein expression. (biomedcentral.com)
  • This study provided evidence that the up-regulation of p27 protein expression is at least in part due to increased synthesis and that this increase fairly faithfully recapitulates the cancer preventive activity of nutritional and chemopreventive anti-cancer agents. (biomedcentral.com)
  • Preliminary studies using in vivo model of MNU-induced rat mammary cancer and in vitro model of cultured cells had suggested - but not proved - that various nutritional and chemopreventive anti-cancer agents, including moderate dietary restriction, up-regulated the expression of p27 (Fig. 1a ). (biomedcentral.com)
  • Indeed, statin induced p27(KIP1) expression by downregulation of histone methyltransferase enhancer of zeste homolog 2 (EZH2), which acts as an epigenetic gene silencer. (nih.gov)
  • Conclusion: Our analysis demonstrated that p27 Kip1 is heterogeneously expressed in renal cell carcinomas. (uni-luebeck.de)
  • Of the 63 tumors evaluated 23 [36.5%] were positive for p27 within the nucleus. (biomedcentral.com)
  • Within cells, p27 is located primarily in the nucleus, where it plays a critical role in controlling cell growth and division. (medlineplus.gov)
  • For example, when p27 is held (sequestered) in the fluid that surrounds the nucleus (the cytoplasm) instead of being transported into the nucleus, the protein is unavailable to block cell cycle progression. (medlineplus.gov)
  • Still other mutations prevent p27 from moving from the cytoplasm into the nucleus. (medlineplus.gov)
  • All of these mutations reduce the amount of functional p27 that is available in the nucleus to regulate the cell cycle. (medlineplus.gov)
  • However, changes in regulation that reduce the amount or function of the p27 protein in the nucleus are found in many types of cancer. (medlineplus.gov)
  • studies suggest that certain endocrine cells may be particularly dependent on the p27 protein to control cell division. (medlineplus.gov)
  • Thus LKB1-AMPK pathway-dependent phosphorylation of p27 at Thr 198 stabilizes p27 and permits cells to survive growth factor withdrawal and metabolic stress through autophagy. (elsevierpure.com)
  • Cell cycle-dependent translation of p27 involves a responsive element in its 5 '-UTR that overlaps with a uORF. (mpg.de)
  • This latter finding is likely to preclude the existence of cryptic transcription factor binding site(s) in the 5'-untranslated region of p27 gene. (biomedcentral.com)
  • The experimental evidence, presented in the second half of this report, was obtained using the 5'-untranslated region (-575) of p27 gene. (biomedcentral.com)
  • To address this question, the effects of various nutritional and chemopreventive anti-cancer agents on the activity of the proximal 5'-upstream region of p27 gene were investigated by transient transfection assay. (biomedcentral.com)
  • Some mutations impair the protein's ability to interact with regulatory proteins, while others lead to the production of an unstable version of p27 that is quickly broken down. (medlineplus.gov)
  • ELAV/Hu proteins inhibit p27 translation via an IRES element in the p27 5 ' UTR. (mpg.de)
  • p27 binds cyclin-CDK complexes through a sequential mechanism involving binding-induced protein folding. (mpg.de)
  • But no significant correlation was found between p27 and other parameters. (biomedcentral.com)
  • The p16(Ink4a) and p19(Arf) knockout mice were generated via transcription activator-like effector nucleases (TALENs), and p27(Kip1) knockout mice via clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRISPR/Cas9). (koreamed.org)
  • C) Semi-quantitative PCR analysis for p27 transcript in the liver of WT and p27Kip1 KO mouse. (koreamed.org)
  • B) A representative result of PCR genotyping for B6 strain of WT and p27Kip1 KO mouse. (koreamed.org)