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Cell-permeable carboxyl-terminal p27(Kip1) peptide exhibits anti-tumor activity by inhibiting Pim-1 kinase.

Morishita D, Takami M, Yoshikawa S, Katayama R, Sato S, Kukimoto-Niino M, Umehara T, Shirouzu M, Sekimizu K, Yokoyama S, Fujita N
J Biol Chem 286 2681-8 (2011)
Cited: 24 times
EuropePMC logo PMID: 21062737

Abstract

The incidence and death rate of prostate cancer is increasing rapidly. In addition, the low sensitivity of prostate cancer to chemotherapy makes it difficult to treat this condition. The serine/threonine kinase Pim-1 plays an important role in cell cycle progression and apoptosis inhibition, resulting in prostate tumorigenesis. Therefore, Pim-1 inhibition has been expected to be an attractive target for developing new anti-cancer drugs. However, no small compounds targeting Pim-1 have progressed to clinical use because of their lack of specificity. Here, we have reported a new cell-permeable Pim-1 inhibitory p27(Kip1) peptide that could interfere with the binding of Pim-1 to its substrates and act as an anti-cancer drug. The peptide could bind to Pim-1 and inhibit phosphorylation of endogenous p27(Kip1) and Bad by Pim-1. Treatment of prostate cancer with the peptide induces G(1) arrest and subsequently apoptosis in vitro. However, the peptide showed almost no growth inhibitory or apoptosis-inducing effects in normal cells. The peptide could inhibit tumor growth in in vivo prostate cancer xenograft models. Moreover, the peptide treatment could overcome resistance to taxol, one of the first line chemotherapeutic agents for prostate cancer, and a combination of the peptide with taxol synergistically inhibited prostate cancer growth in vivo. These results indicate that a Pim-1 inhibitory p27(Kip1) peptide could be developed as an anti-cancer drug against prostate cancer.

Articles - 3a99 mentioned but not cited (9)

  1. A water-mediated allosteric network governs activation of Aurora kinase A. Cyphers S, Ruff EF, Behr JM, Chodera JD, Levinson NM. Nat Chem Biol 13 402-408 (2017)
  2. Identification of the first inhibitor of the GBP1:PIM1 interaction. Implications for the development of a new class of anticancer agents against paclitaxel resistant cancer cells. Andreoli M, Persico M, Kumar A, Orteca N, Kumar V, Pepe A, Mahalingam S, Alegria AE, Petrella L, Sevciunaite L, Camperchioli A, Mariani M, Di Dato A, Novellino E, Scambia G, Malhotra SV, Ferlini C, Fattorusso C. J Med Chem 57 7916-7932 (2014)
  3. Cell-permeable carboxyl-terminal p27(Kip1) peptide exhibits anti-tumor activity by inhibiting Pim-1 kinase. Morishita D, Takami M, Yoshikawa S, Katayama R, Sato S, Kukimoto-Niino M, Umehara T, Shirouzu M, Sekimizu K, Yokoyama S, Fujita N. J Biol Chem 286 2681-2688 (2011)
  4. A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs). Ehrt C, Brinkjost T, Koch O. PLoS Comput Biol 14 e1006483 (2018)
  5. Analysis of protein binding sites by computational solvent mapping. Hall DR, Kozakov D, Vajda S. Methods Mol Biol 819 13-27 (2012)
  6. Flexibility of the P-loop of Pim-1 kinase: observation of a novel conformation induced by interaction with an inhibitor. Parker LJ, Watanabe H, Tsuganezawa K, Tomabechi Y, Handa N, Shirouzu M, Yuki H, Honma T, Ogawa N, Nagano T, Yokoyama S, Tanaka A. Acta Crystallogr Sect F Struct Biol Cryst Commun 68 860-866 (2012)
  7. New Quinoxaline Derivatives as Dual Pim-1/2 Kinase Inhibitors: Design, Synthesis and Biological Evaluation. Oyallon B, Brachet-Botineau M, Logé C, Robert T, Bach S, Ibrahim S, Raoul W, Croix C, Berthelot P, Guillon J, Pinaud N, Gouilleux F, Viaud-Massuard MC, Denevault-Sabourin C. Molecules 26 867 (2021)
  8. The dipeptidyl peptidase IV inhibitors vildagliptin and K-579 inhibit a phospholipase C: a case of promiscuous scaffolds in proteins. Chakraborty S, Rendón-Ramírez A, Ásgeirsson B, Dutta M, Ghosh AS, Oda M, Venkatramani R, Rao BJ, Dandekar AM, Goñi FM. F1000Res 2 286 (2013)
  9. Dibenzofuran Derivatives Inspired from Cercosporamide as Dual Inhibitors of Pim and CLK1 Kinases. Dao VH, Ourliac-Garnier I, Logé C, McCarthy FO, Bach S, da Silva TG, Denevault-Sabourin C, Thiéfaine J, Baratte B, Robert T, Gouilleux F, Brachet-Botineau M, Bazin MA, Marchand P. Molecules 26 6572 (2021)


Reviews citing this publication (6)

  1. PIM Kinase as an Executional Target in Cancer. Zhang X, Song M, Kundu JK, Lee MH, Liu ZZ. J Cancer Prev 23 109-116 (2018)
  2. Roles of Pim-3, a novel survival kinase, in tumorigenesis. Mukaida N, Wang YY, Li YY. Cancer Sci 102 1437-1442 (2011)
  3. The oncogenic PIM kinase family regulates drug resistance through multiple mechanisms. Isaac M, Siu A, Jongstra J. Drug Resist Updat 14 203-211 (2011)
  4. Pathophysiological roles of Pim-3 kinase in pancreatic cancer development and progression. Li YY, Mukaida N. World J Gastroenterol 20 9392-9404 (2014)
  5. Insights from Pim1 structure for anti-cancer drug design. Ogawa N, Yuki H, Tanaka A. Expert Opin Drug Discov 7 1177-1192 (2012)
  6. A systematic review on active sites and functions of PIM-1 protein. Zhao Y, Aziz AUR, Zhang H, Zhang Z, Li N, Liu B. Hum Cell 35 427-440 (2022)

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  1. Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials. Lin A, Giuliano CJ, Palladino A, John KM, Abramowicz C, Yuan ML, Sausville EL, Lukow DA, Liu L, Chait AR, Galluzzo ZC, Tucker C, Sheltzer JM. Sci Transl Med 11 eaaw8412 (2019)
  2. RNAi screen identifies a synthetic lethal interaction between PIM1 overexpression and PLK1 inhibition. van der Meer R, Song HY, Park SH, Abdulkadir SA, Roh M. Clin Cancer Res 20 3211-3221 (2014)
  3. Selective bisubstrate inhibitors with sub-nanomolar affinity for protein kinase Pim-1. Ekambaram R, Enkvist E, Vaasa A, Kasari M, Raidaru G, Knapp S, Uri A. ChemMedChem 8 909-913 (2013)
  4. Computational analysis of benzofuran-2-carboxlic acids as potent Pim-1 kinase inhibitors. Wadood A, Jamal SB, Riaz M, Mir A. Pharm Biol 52 1170-1178 (2014)
  5. Interferon-γ-induced p27KIP1 binds to and targets MYC for proteasome-mediated degradation. Bahram F, Hydbring P, Tronnersjö S, Zakaria SM, Frings O, Fahlén S, Nilsson H, Goodwin J, von der Lehr N, Su Y, Lüscher B, Castell A, Larsson LG. Oncotarget 7 2837-2854 (2016)
  6. Kinase crystal identification and ATP-competitive inhibitor screening using the fluorescent ligand SKF86002. Parker LJ, Taruya S, Tsuganezawa K, Ogawa N, Mikuni J, Honda K, Tomabechi Y, Handa N, Shirouzu M, Yokoyama S, Tanaka A. Acta Crystallogr D Biol Crystallogr 70 392-404 (2014)
  7. Dipyrithione induces cell-cycle arrest and apoptosis in four cancer cell lines in vitro and inhibits tumor growth in a mouse model. Fan Y, Liu C, Huang Y, Zhang J, Cai L, Wang S, Zhang Y, Duan X, Yin Z. BMC Pharmacol Toxicol 14 54 (2013)
  8. Effect of p27 gene combined with Pientzehuang ([characters: see text]) on tumor growth in osteosarcoma-bearing nude mice. Ren SS, Yuan F, Liu YH, Zhou LT, Li J. Chin J Integr Med 21 830-836 (2015)
  9. Motor activity of centromere-associated protein-E contributes to its localization at the center of the midbody to regulate cytokinetic abscission. Ohashi A, Ohori M, Iwai K. Oncotarget 7 79964-79980 (2016)


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