Poly-ADP ribosylation of p21 by tankyrases promotes p21 degradation and regulates cell cycle progression

Misun Jung, Wonyoung Kim, Jin Won Cho, Won Ho Yang, In Kwon Chung

Research output: Contribution to journalArticlepeer-review


p21WAF1/Cip1 acts as a key negative regulator of cell cycle progression, which can form complexes with cyclin-dependent kinases together with specific cyclins to induce cell cycle arrest at specific stages. p21 protein levels have been shown to be regulated primarily through phosphorylation and ubiquitination during various stages of the cell cycle. Although phosphorylation and ubiquitin-dependent proteasomal degradation of p21 have been well established, other post-translational modifications that contribute to regulation of p21 stability and function remain to be further elucidated. Here, we show that p21 degradation and its function are controlled by tankyrases, which are members of the poly (ADP-ribose) polymerase (PARP) protein family. p21 interacts with tankyrases via newly defined tankyrase-binding motifs and is PARylated by tankyrases in vitro and in vivo, suggesting that PARylation is a new post-translational modification of p21. Up-regulation of tankyrases induces ubiquitin-dependent proteasomal degradation of p21 through an E3 ligase RNF146, thus promoting cell cycle progression in the G1/S phase transition. On the contrary, inhibition of tankyrases by knockdown or inhibitor treatment stabilizes p21 protein and leads to cell cycle arrest in the G1 phase. Together, our data demonstrate that tankyrase may function as a new molecular regulator that controls the protein levels of p21 through PARylation-dependent proteasomal degradation. Hence, a novel function of the tankyrase-p21 axis may represent a new avenue for regulating cell cycle progression.

Original languageEnglish
Pages (from-to)2379-2394
Number of pages16
JournalBiochemical Journal
Issue number22
Publication statusPublished - 2022 Nov

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation of Korea (2016R1A5A1010764 and 2018R1A2B6005299 to I.K.C.).

Publisher Copyright:
© 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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