Protein Information

Name cyclin dependent kinase (protein family or complex)
Synonyms cyclin dependent kinase; cyclin dependent kinases

Compound Information

Name cycloheximide
CAS

Reference List

PubMed Abstract RScore(About this table)
15870436 Van Dross R, Yao S, Asad S, Westlake G, Mays DJ, Barquero L, Duell S, Pietenpol JA, Browning PJ: Constitutively active K-cyclin/cdk6 kinase in Kaposi sarcoma-associated herpesvirus-infected cells. J Natl Cancer Inst. 2005 May 4;97(9):656-66.

BACKGROUND: Kaposi sarcoma-associated human herpesvirus (KSHV) encodes K-cyclin, a homologue of D-type cellular cyclins, which binds cyclin-dependent kinases to phosphorylate various substrates.
The half-life of K-cyclin and cyclin D2 proteins was determined by blocking protein synthesis with cycloheximide and measuring proteins in cell lysates by western blot analysis.
2(0,0,0,2) Details
17407140 Fu Y, Fang Z, Liang Y, Zhu X, Prins P, Li Z, Wang L, Sun L, Jin J, Yang Y, Zha X: Overexpression of integrin beta1 inhibits proliferation of hepatocellular carcinoma cell SMMC-7721 through preventing Skp2-dependent degradation of p27 via PI3K pathway. J Cell Biochem. 2007 Oct 15;102(3):704-18.

Here we reported that one of the cyclin-dependent kinase (CDK) inhibitors, p27 (Kip1) was involved in proliferation-inhibition induced by overexpression of integrin beta1.
Cycloheximide (Chx) treatment and pulse-chase experiments revealed that overexpression of integrin beta1 prolonged the half-life of p27 (Kip1) by inhibiting its degradation.
1(0,0,0,1) Details
16452462 Jelinkova L, Kubelka M: Neither Aurora B activity nor histone H3 phosphorylation is essential for chromosome condensation during meiotic maturation of porcine oocytes. Biol Reprod. 2006 May;74(5):905-12. Epub 2006 Feb 1.

Treatment of oocytes with 50 microM butyrolactone I (BL-I), an inhibitor of cyclin-dependent kinases, or cycloheximide (10 microg/ml), inhibitor of proteosynthesis, results in a block of oocytes in the germinal vesicle stage, when nuclear membrane remains intact; however, condensed chromosome fibers or highly condensed chromosome bivalents can be seen in the nucleoplasm of BL-I- or cycloheximide-treated oocytes, respectively.
31(0,1,1,1) Details
15545300 Jaruga-Killeen E, Rayford W: TNF receptor 1 is involved in the induction of apoptosis by the cyclin dependent kinase inhibitor p27Kip1 in the prostate cancer cell line PC-3. FASEB J. 2005 Jan;19(1):139-41. Epub 2004 Nov 15.

Cell cycle and typical markers of apoptosis were analyzed by flow cytometry in the presence of the following reagents: cycloheximide, pan-caspase inhibitor ZVAD-fmk, neutralizing anti-TNFR1, and anti-TNFR2.
2(0,0,0,2) Details
15753078 Arbel-Goren R, Levy Y, Ronen D, Zick Y: Cyclin-dependent kinase inhibitors and JNK act as molecular switches, regulating the choice between growth arrest and apoptosis induced by galectin-8. J Biol Chem. 2005 May 13;280(19):19105-14. Epub 2005 Mar 7.

When p21 expression was inhibited by cycloheximide, galectin-8 directed the cells toward apoptosis, which involves induction of poly (ADP-ribose) polymerase cleavage.
2(0,0,0,2) Details
19016568 Malone JL, Nelson AC, Lieberman R, Anderson S, Holt JT: Oestrogen-mediated phosphorylation and stabilization of BRCA2 protein in breast. J Pathol. 2009 Feb;217(3):380-8.

This increase seen in BRCA2 total and phospho-S3291 protein levels was found to be unaffected with cycloheximide pre-treatment, but decreased following tamoxifen, ICI 182,780 or roscovitine treatment.
This suggests a requirement for ER and cdk (cyclin-dependent kinase) in mediating the increased protein levels.
1(0,0,0,1) Details
17266789 Toranzo GS, Bonilla F, Zelarayan L, Oterino J, Buhler MI: Activation of maturation promoting factor in Bufo arenarum oocytes: injection of mature cytoplasm and germinal vesicle contents. Zygote. 2006 Nov;14(4):305-16.


Reinitiation of meiosis is regulated by maturation promoting factor (MPF), a complex of the cyclin-dependent kinase p34cdc2 and cyclin B.
1(0,0,0,1) Details
15964852 Zhu H, Nie L, Maki CG: Cdk2-dependent Inhibition of p21 stability via a C-terminal cyclin-binding motif. J Biol Chem. 2005 Aug 12;280(32):29282-8. Epub 2005 Jun 17.


p21 is a member of the Cip/Kip family of cyclin-dependent kinase (CDK) inhibitors that includes p21, p27, and p57.
1(0,0,0,1) Details
18784249 Ajduk A, Ciemerych MA, Nixon V, Swann K, Maleszewski M: Fertilization differently affects the levels of cyclin B1 and M-phase promoting factor activity in maturing and metaphase II mouse oocytes. Reproduction. 2008 Dec;136(6):741-52. Epub 2008 Sep 10.


In metaphase II oocytes, it leads to a Ca (2)(+)-dependent, continuous degradation of cyclin B1 and inactivation of cyclin dependent kinase (CDC2A)-cyclin B1 complex (MPF).
1(0,0,0,1) Details
19009649 Guller M, Toualbi-Abed K, Legrand A, Michel L, Mauviel A, Bernuau D, Daniel F: c-Fos overexpression increases the proliferation of human hepatocytes by stabilizing nuclear Cyclin D1. World J Gastroenterol. 2008 Nov 7;14(41):6339-46.

The levels of cell cycle regulatory proteins (Cyclin D1, E, A) cyclin dependent kinases (cdk) cdk2, cdk4, cdk6, and their inhibitors p15, p16, p21, p27, total and phosphorylated GSK-3beta and epidermal growth factor receptor (EGF-R) were assayed by Western blotting.
Stability of Cyclin D1 was studied by cycloheximide blockade experiments.
1(0,0,0,1) Details
16407831 Taube ME, Liu XW, Fridman R, Kim HR: TIMP-1 regulation of cell cycle in human breast epithelial cells via stabilization of p27 (KIP1) protein. Oncogene. 2006 May 18;25(21):3041-8.


TIMP-1-mediated cell cycle arrest is associated with its downregulation of cyclin D (1) and upregulation of p27 (KIP1), resulting in inhibition of cyclin-dependent kinase activity necessary for phosphorylation of the tumor suppressor retinoblastoma protein.
1(0,0,0,1) Details
19424645 Lee EY, Jeon MJ, Yang W, Shin I: Effect of p27 on motility of MDA-MB-231 breast cancer cells. Oncol Rep. 2009 Jun;21(6):1621-5.

p27 is a member of the Kip family of cyclin-dependent kinase inhibitors and its overexpression results in cell cycle arrest at G1 and/or apoptosis.
Wound healing assays revealed that migration of MDA-MB-231 hpshRNA cells was markedly impaired compared to MDA-MB-231 mpshRNA cells, especially when cycloheximide was added to block protein synthesis.
1(0,0,0,1) Details
17329956 Matsumoto E, Hatanaka M, Bohgaki M, Maeda S: PKC pathway and ERK/MAPK pathway are required for induction of cyclin D1 and p21Waf1 during 12-o-tetradecanoylphorbol 13-acetate-induced differentiation of myeloleukemia cells. Kobe J Med Sci. 2006;52(6):181-94.


The upregulation of p21Waf1 seems to play a critical role in TPA-induced cell differentiation by suppressing cyclin dependent kinase activity , while the upregulation of cyclin D1 seems to be compensated by p21Waf1.
1(0,0,0,1) Details
18204075 Cucciolla V, Borriello A, Criscuolo M, Sinisi AA, Bencivenga D, Tramontano A, Scudieri AC, Oliva A, Zappia V, Della Ragione F: Histone deacetylase inhibitors upregulate p57Kip2 level by enhancing its expression through Sp1 transcription factor. Carcinogenesis. 2008 Mar;29(3):560-7. Epub 2008 Jan 19.

Here, we evaluate the effects of butyrate (BuA) and other HDACIs on p57 (Kip2), a cyclin-dependent kinase inhibitor (cki).
The cki upregulation is associated with an increased gene expression that was not prevented by cycloheximide, indicating that HDACIs affect directly p57 (Kip2) transcription.
1(0,0,0,1) Details
18721791 Nam M, Lee WH, Bae EJ, Kim SG: Compound C inhibits clonal expansion of preadipocytes by increasing p21 level irrespectively of AMPK inhibition. Arch Biochem Biophys. 2008 Nov 1;479(1):74-81. Epub 2008 Aug 9.

CC treatment blocked hormone-induced preadipocyte differentiation due to inhibition of mitotic clonal expansion, which was accompanied by the failure of degradation of p21, a cyclin-dependent kinase inhibitor.
Cycloheximide decreased the basal p21 level, which was inhibited by CC treatment, supporting the stabilization of p21 by CC.
1(0,0,0,1) Details
17173074 Ma Y, Cress WD: Transcriptional upregulation of p57 (Kip2) by the cyclin-dependent kinase inhibitor BMS-387032 is E2F dependent and serves as a negative feedback loop limiting cytotoxicity. Oncogene. 2007 May 24;26(24):3532-40. Epub 2006 Dec 18.

In spite of the fact that cyclin-dependent kinase (cdk) inhibiting drugs are potent transcriptional repressors, we discover that p57 (Kip2, CDKN1C) transcription is significantly upregulated by three small molecule cdk inhibitors, including BMS-387032.
An E2F1-estrogen receptor fusion protein activated the endogenous p57 promoter in response to hydroxytamoxifen treatment in the presence of cycloheximide.
1(0,0,0,1) Details