The mechanisms of PML-nuclear body formation.
PML nuclear bodies (NBs) are nuclear structures that have been implicated in processes such as transcriptional regulation, genome stability, response to viral infection, apoptosis, and tumor suppression. PML has been found to be essential for the formation of the NBs, as these structures do not form in Pml null cells, although PML add back fully rescues their formation. However, the basis for such a structural role of PML is unknown. We demonstrate that PML contains a SUMO binding motif that is independent of its SUMOylation sites and is surprisingly necessary for PML-NB formation. We demonstrate that the PML RING domain is critical for PML SUMOylation and PML-NB formation. We propose a model for PML-NB formation whereby PML SUMOylation and noncovalent binding of PML to SUMOylated PML through the SUMO binding motif constitutes the nucleation event for subsequent recruitment of SUMOylated proteins and/or proteins containing SUMO binding motifs to the PML NBs.
Shen
Tian Huai
TH
Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Lin
Hui-Kuan
HK
Scaglioni
Pier Paolo
PP
Yung
Thomas M
TM
Pandolfi
Pier Paolo
PP
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002461:Cell Line, Transformed; D022003:Cell Nucleus Structures / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000473:pathology; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D025842:SUMO-1 Protein / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*
D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D025842:SUMO-1 Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins