API

Event: 1505

Key Event Title

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Cell cycle, disrupted

Short name

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Cell cycle, disrupted

Biological Context

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Level of Biological Organization
Cellular

Cell term

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Cell term
cell


Organ term

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Organ term
organ


Key Event Components

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Process Object Action
regulation of cell cycle cell cycle-related cyclin disrupted

Key Event Overview


AOPs Including This Key Event

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AOP Name Role of event in AOP
Histone deacetylase inhibition leading to testicular atrophy KeyEvent

Stressors

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Taxonomic Applicability

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Term Scientific Term Evidence Link
Homo sapiens Homo sapiens High NCBI
Mus musculus Mus musculus High NCBI

Life Stages

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Life stage Evidence
Not Otherwise Specified Moderate

Sex Applicability

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Term Evidence
Unspecific High

Key Event Description

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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

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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

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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].


References

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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