Title: PARP14 regulates cyclin D1 expression to promote cell-cycle progression.
Authors: O'Connor, Michael J; Thakar, Tanay; Nicolae, Claudia M; Moldovan, George-Lucian
Published In Oncogene, (2021 07)
Abstract: Cyclin D1 is an essential regulator of the G1-S cell-cycle transition and is overexpressed in many cancers. Expression of cyclin D1 is under tight cellular regulation that is controlled by many signaling pathways. Here we report that PARP14, a member of the poly(ADP-ribose) polymerase (PARP) family, is a regulator of cyclin D1 expression. Depletion of PARP14 leads to decreased cyclin D1 protein levels. In cells with a functional retinoblastoma (RB) protein pathway, this results in G1 cell-cycle arrest and reduced proliferation. Mechanistically, we found that PARP14 controls cyclin D1 mRNA levels. Using luciferase assays, we show that PARP14 specifically regulates cyclin D1 3'UTR mRNA stability. Finally, we also provide evidence that G1 arrest in PARP14-depleted cells is dependent on an intact p53-p21 pathway. Our work uncovers a new role for PARP14 in promoting cell-cycle progression through both cyclin D1 and the p53 pathway.
PubMed ID: 34158578
MeSH Terms: 3' Untranslated Regions; Cell Cycle/genetics*; Cell Line; Cyclin D1/genetics*; Cyclin D1/metabolism; E2F1 Transcription Factor; G1 Phase Cell Cycle Checkpoints/genetics; Gene Expression Regulation*; Gene Knockdown Techniques; Humans; Poly(ADP-ribose) Polymerases/metabolism*; RNA Interference; RNA Stability; RNA, Messenger/genetics; RNA, Small Interfering/genetics; Retinoblastoma Protein/metabolism