PML3 interacts with TRF1 and is essential for ALT-associated PML bodies assembly in U2OS cells

Yu, Jian; Lan, Jianping; Wang, Chong; Wu, Quan; Zhu, Yuanyuan; Lai, Xiaoyu; Sun, Jie; Jin, Changjiang; Huang, He

doi:10.1016/j.canlet.2009.10.009

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Volume 291, Issue 2 , Pages 177-186, 28 May 2010

PML3 interacts with TRF1 and is essential for ALT-associated PML bodies assembly in U2OS cells

Jian Yu
- The First Affiliated Hospital of Zhejiang University Medical School, Hangzhou 310003, China
- Anhui Key Laboratory for Cellular Dynamics and Chemical Biology and National Laboratory for Physical Sciences at Nanoscale, Hefei 230027, China
- These authors contributed equally to this work.
Jianping Lan
- The First Affiliated Hospital of Zhejiang University Medical School, Hangzhou 310003, China
- Department of Hematology, Zhejiang Provincial People’s Hospital, Hangzhou 310014, China
- Anhui Key Laboratory for Cellular Dynamics and Chemical Biology and National Laboratory for Physical Sciences at Nanoscale, Hefei 230027, China
- These authors contributed equally to this work.
Chong Wang
- The First Affiliated Hospital of Zhejiang University Medical School, Hangzhou 310003, China
Quan Wu
- Anhui Key Laboratory for Cellular Dynamics and Chemical Biology and National Laboratory for Physical Sciences at Nanoscale, Hefei 230027, China
Yuanyuan Zhu
- The First Affiliated Hospital of Zhejiang University Medical School, Hangzhou 310003, China
Xiaoyu Lai
- The First Affiliated Hospital of Zhejiang University Medical School, Hangzhou 310003, China
Jie Sun
- The First Affiliated Hospital of Zhejiang University Medical School, Hangzhou 310003, China
Changjiang Jin
- Anhui Key Laboratory for Cellular Dynamics and Chemical Biology and National Laboratory for Physical Sciences at Nanoscale, Hefei 230027, China
- Corresponding authors. Tel./fax: +86 571 8723 6706 (H. Huang), +86 551 360 7141 (C. Jin).
He Huang
- The First Affiliated Hospital of Zhejiang University Medical School, Hangzhou 310003, China
- Corresponding authors. Tel./fax: +86 571 8723 6706 (H. Huang), +86 551 360 7141 (C. Jin).

Received 17 May 2009; received in revised form 11 October 2009; accepted 13 October 2009. published online 09 November 2009.

Abstract

Telomerase-negative cancer cells maintain their telomeres by a mechanism known as alternative lengthening of telomeres (ALT) and achieve unlimited replicative potential. A hallmark of ALT cells is the recruitment of telomeres to promyelocytic leukemia (PML) bodies and formation of ALT-associated PML bodies (APBs). Although the exact molecular mechanism of APBs assembly remains unclear, APBs assembly requires telomere and PML body-associated proteins, including TRF1 and PML. Here, we report that PML3, one of PML isoforms, is involved in APBs formation. As a new binding protein of TRF1 (telomeric repeat binding factor 1), PML3 directly interacts with TRF1 and recruits TRF1 to PML bodies in U2OS cells. More notably, depletion of PML3 by small interfering RNA does not affect PML bodies formation, but inhibits the recruitment of both TRF1 and TRF2 to APBs. Further study shows that the recruitment of TRF1 to APBs depends on its interaction with a specific PML3 isoform. Thus, the interaction of PML3 with TRF1 is isoform specific and likely to be essential for APBs assembly in U2OS cells.

Keywords: Alternative lengthening of telomeres, ALT-associated PML bodies, TRF1, PML3