ARTD1 regulates cyclin E expression and consequently cell-cycle re-entry and G1/S progression in T24 bladder carcinoma cells.

Abstract

ADP-ribosylation is involved in a variety of biological processes, many of which are chromatin-dependent and linked to important functions during the cell cycle. However, any study on ADP-ribosylation and the cell cycle faces the problem that synchronization with chemical agents or by serum starvation and subsequent growth factor addition already activates ADP-ribosylation by itself. Here, we investigated the functional contribution of ARTD1 in cell cycle re-entry and G1/S cell cycle progression using T24 urinary bladder carcinoma cells, which synchronously re-enter the cell cycle after splitting without any additional stimuli. In synchronized cells, ARTD1 knockdown, but not inhibition of its enzymatic activity, caused specific down-regulation of cyclin E during cell cycle re-entry and G1/S progression through alterations of the chromatin composition and histone acetylation, but not of other E2F-1 target genes. Although Cdk2 formed a functional complex with the residual cyclin E, p27(Kip 1) protein levels increased in G1 upon ARTD1 knockdown most likely due to inappropriate cyclin E-Cdk2-induced phosphorylation-dependent degradation, leading to decelerated G1/S progression. These results provide evidence that ARTD1 regulates cell cycle re-entry and G1/S progression via cyclin E expression and p27(Kip 1) stability independently of its enzymatic activity, uncovering a novel cell cycle regulatory mechanism.

• Authors: Karolin Léger, Ann-Katrin Hopp, Monika Fey, Michael O Hottiger
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 15 Issue 15 Pg. 2042-52 (Aug 02 2016) ISSN: 1551-4005 [Electronic] United States
• PMID: 27295004 (Publication Type: Journal Article)

Chemical References

• CCNE1 protein, human
• Cyclin E
• E2F1 Transcription Factor
• E2F1 protein, human
• Oncogene Proteins
• Cyclin-Dependent Kinase Inhibitor p27
• PARP1 protein, human
• Poly (ADP-Ribose) Polymerase-1
• CDK2 protein, human
• Cyclin-Dependent Kinase 2

Topics

• Cell Line, Tumor
• Cyclin E (metabolism)
• Cyclin-Dependent Kinase 2 (metabolism)
• Cyclin-Dependent Kinase Inhibitor p27 (metabolism)
• Down-Regulation (genetics)
• E2F1 Transcription Factor (metabolism)
• G1 Phase
• Gene Knockdown Techniques
• Humans
• Oncogene Proteins (metabolism)
• Phosphorylation
• Poly (ADP-Ribose) Polymerase-1 (metabolism)
• Promoter Regions, Genetic (genetics)
• S Phase
• Transcription, Genetic
• Urinary Bladder Neoplasms (metabolism, pathology)