Two-step colocalization of MORC3 with PML nuclear bodies.
Many functional subdomains, including promyelocytic leukemia nuclear bodies (PML NBs), are formed in the mammalian nucleus. Various proteins are constitutively or transiently accumulated in PML NBs in a PML-dependent manner. MORC3 (microrchidia family CW-type zinc-finger 3), also known as NXP2, which consists of GHL-ATPase, a CW-type zinc-finger and coiled-coil domains, is localized in PML NBs, where it recruits and activates p53 to induce cellular senescence. Interestingly, we found that MORC3 can form PML-independent nuclear domains (NDs) in mouse hematopoietic cells and even in Pml-deficient cells. Here, we show that MORC3 colocalizes with PML by a two-step molecular mechanism: the PML-independent formation of MORC3 NDs by the ATPase cycle, and the association of MORC3 with PML via the SUMO1-SUMO-interacting motif (SIM). Similarly to other members of the GHL-ATPase family, MORC3 functions as a 'molecular clamp'. ATP binding induces conformational changes in MORC3, leading to the formation of MORC3 NDs, and subsequent ATP hydrolysis mediates the diffusion and binding of MORC3 to the nuclear matrix. MORC3 might clamp DNA or nucleosomes in MORC3 NDs via the CW domain. Furthermore, the SUMOylation of MORC3 at five sites was involved in the association of MORC3 with PML, and SUMO1-unmodified MORC3 formed NDs independently of PML.
Mimura
Yasuhiro
Y
Department of Molecular Genetics, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
Takahashi
Keiko
K
Kawata
Kiyo
K
Akazawa
Takashi
T
Inoue
Norimitsu
N
D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000737:chemistry / Q000378:metabolism*; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D025842:SUMO-1 Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D000251:Adenosine Triphosphatases; C551732:MORC3 protein, human; C551731:MORC3 protein, mouse