The main components of RB pathway involves five family proteins; retinoblastoma tumor suppressor RB- family of pocket proteins (p110, p107, p130), E2F-family of transcription factors (heterodimers of E2F1-8 with DP1-2), cyclins (D and E-type), cyclin-dependent protein kinases (cdk4, cdk6) and cyclin-dependent kinase
inhibitor CDKIs (p16Ink4a, p15Ink4b, p18Ink4c and p19Ink4d).
Abbreviations: CDK, cyclin-dependent kinase
; CHX, cycloheximide; ERK1/2, extracellular signal-regulated kinasesl/2; GSK3[beta], glycogen synthase kinase 3 beta: 1[kappa]/K-[alpha], 1[kappa]B kinase-[alpha]; JNK, c-Jun N-terminal kinases; LMB, leptomycin B; MRB, mulberry root bark extracts; MTT, 3-(4,5-dimethylthizaol-2-yl)-2,5-diphenyl tetrazolium bromide.
Mulner et al., "Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases
cdc2, cdk2 and cdk5," European Journal of Biochemistry, vol.
Meijer, "Pharmacological inhibitors of cyclin-dependent kinases
," Trends in Pharmacological Sciences, vol.
Harlow, "Distinct roles for cyclin-dependent kinases
in cell cycle control," Science, vol.
Johnson, "Cyclin-dependent kinases
regulate apoptosis of intestinal epithelial cells," Apoptosis, vol.
At day 1 after enucleation, 85 genes have been up-/downregulated, while at day 15 of the process only 7 such genes have been found, among them genes directly involved in cell cycle regulation, for example, cyclins (cyclin E1, E2, and B1), cyclin-dependent kinases
(Cdk6 and Cdk1)--enzymes that regulate transcription, mRNA processing and progression of cell cycle, also enzymes involved in separation of sister chromatids during anaphase, centromere proteins (Cenpe and Cenpf), and kinetochore proteins (Ska3).
Kenpaullone impedes the action of proteins called cyclin-dependent kinases
, which affect nerve cell growth and many other cell functions.
(28.) Malumbres M, Barbacid M: Mammalian cyclin-dependent kinases
. Trends Biochem Sci 2005; 30: 630-641
regulate the antiproliferative function of Smads.
Abnormal expression of cyclin D1 and cyclin-dependent kinases
(CDKs) have been considered to be one of the most important factors in the tumourigenesis of various human malignancies.
Among the topics discussed are the QSAR computational model for identifying cyclin-dependent kinases
as a therapeutic target in lung cancer, molecular analysis of genetic risk factors for benign prostatic hyperplasia (BPH), and the relationship between obesity and cancer.