PARP14 regulates cyclin D1 expression to promote cell-cycle progression

被引：46

作者：

O'Connor, Michael J. ^{[1
]}

Thakar, Tanay ^{[1
]}

Nicolae, Claudia M. ^{[1
]}

Moldovan, George-Lucian ^{[1
]}

机构：

[1] Penn State Univ, Coll Med, Dept Biochem & Mol Biol, Hershey, PA 17033 USA

来源：

ONCOGENE | 2021年 / 40卷 / 30期

关键词：

TUMOR-SUPPRESSOR; FAMILY; CANCER; GENE; P21; P53; PROLIFERATION; INHIBITION; DYNAMICS; PARP-14;

D O I：

10.1038/s41388-021-01881-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：4872 / 4883

页数：12

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