PML3 interacts with TRF1 and is essential for ALT-associated PML bodies assembly in U2OS cells.
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.
Yu
Jian
J
The First Affiliated Hospital of Zhejiang University Medical School, Hangzhou 310003, China.
Lan
Jianping
J
Wang
Chong
C
Wu
Quan
Q
Zhu
Yuanyuan
Y
Lai
Xiaoyu
X
Sun
Jie
J
Jin
Changjiang
C
Huang
He
H
D002453:Cell Cycle; D018076:DNA, Complementary / Q000235:genetics; D005455:Fluorescent Antibody Technique; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018895:Microsatellite Repeats; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D014066:Palatine Tonsil / Q000378:metabolism; D000071156:Promyelocytic Leukemia Protein; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D035321:Telomeric Repeat Binding Protein 1 / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D018076:DNA, Complementary; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D035321:Telomeric Repeat Binding Protein 1; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D005982:Glutathione Transferase