Key Event Title
|Level of Biological Organization|
Key Event Components
|regulation of cell cycle||cell cycle-related cyclin||disrupted|
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP|
|Histone deacetylase inhibition leading to testicular atrophy||KeyEvent|
|Homo sapiens||Homo sapiens||High||NCBI|
|Mus musculus||Mus musculus||High||NCBI|
|Not Otherwise Specified||Moderate|
Key Event Description
The dysregulation of cell cycle leads to the decreases in cell number. The cell cycle consists of G1, S, G2, M, and G0 phase. The cell cyle regulation is disrupted by the cell cycle arrest in certain cell cycle phase. The histone gene expression is regulated in cell cyle phases [Heintz, 1983]. The phosphorylation of p21 (CDKN1A; cyclin dependent kinase inhibitor 1A) regulates its function [Moussa, 2015, Child, 2006]. The up-regulation of p21 level in iron-chelated cancer cells was observed [Moussa, 2015].
How It Is Measured or Detected
The percentage of cells at G1, G0, S, and G2/M phases was determined by flow cytometry analysis using DNA content frequency histogram deconvolution software [Li, 2013].
Cell cycle distribution was analyzed by fluorescence-activated cell sorter (FACS) analysis with a Partec PAS-II sorter [Zupkovitz, 2010].
The four cell cycle phases in living cells can be measured with four-color fluorescent proteins using live cell imaging [Bajar, 2016].
The incorporation of [3H]deoxycytidine or [3H]thymidine into cell DNA during S phase can be monitored as DNA synthesis [Heintz, 1982].
Domain of Applicability
The relationship between disrupted cell cycle and apoptosis is likely well conserved between species.
・The change in the amounts of cells in G1 phase and S phase of cell cycle was detected in mouse HDAC1 knock out fibroblast lines (Mus musculus) [Zupkovitz, 2010].
・The histone gene expression alters in each phase of cell cycle in human HeLa cell (Homo sapiens) [Heintz, 1982].
Heintz N et al. (1983) Regulation of human histone gene expression: Kinetics of accumulation and changes in the rate of synthesis and in the half-lives of individual histone mRNAs during the HeLa cell cycle. Molecular and Cellular Biology 3:539-550
Moussa RS et al. (2015) Differential targeting of the cyclin-dependent kinase inhibitor, p21CIP/WAF1, by chelators with anti-proliferative activity in a range of tumor cell-types. Oncotarget 6:29694-29711
Child ES and Mann DJ. (2006) The intricacies of p21 phosphorylation. Cell Cycle 5:1313-1319
Li Q, Lambrechts MJ, Zhang Q, Liu S, Ge D, Yin R, Xi M and You Z. Glyphosate and AMPA inhibit cancer cell growth through inhibiting intracellular glycine synthesis. Drug Des Devel Ther 2013; 7: 635-643.
Zupkovitz G et al. (2010) The cyclin-dependent kinase inhibitor p21 is a crucial target for histone deacetylase 1 as a regulator of cellular proliferation. Mol Cell Biol 30:1171-1181
Bajar BT et al. (2016) Fluorescent indicators for simultaneous reporting of all four cell cycle phases. Nat Methods 13: 993-996