Functions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumor suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. Acts as the scaffold of PML-NBs allowing other proteins to shuttle in and out, a process which is regulated by SUMO-mediated modifications and interactions. Positively regulates p53/TP53 by acting at different levels (by promoting its acetylation and phosphorylation and by inhibiting its MDM2-dependent degradation). Regulates phosphorylation of ITPR3 and plays a role in the regulation of calcium homeostasis at the endoplasmic reticulum. Regulates RB1 phosphorylation and activity. Acts as both a negative regulator of PPARGC1A acetylation and a potent activator of PPAR signaling and fatty acid oxidation. Regulates translation of HIF1A by sequestering MTOR, and thereby plays a role in neoangiogenesis and tumor vascularization. Regulates PER2 nuclear localization and circadian function. Cytoplasmic PML is involved in the regulation of the TGF-beta signaling pathway. Required for normal development of the brain cortex during embryogenesis. Plays a role in granulopoiesis or monopoiesis of myeloid progenitor cells. May play a role regulating stem and progenitor cell fate in tissues as diverse as blood, brain and breast. Shows antiviral activity towards lymphocytic choriomeningitis virus (LCMV) and the vesicular stomatitis virus (VSV). Key component of PML bodies. PML bodies are formed by the interaction of PML homodimers (via SUMO-binding motif) with sumoylated PML, leading to the assembly of higher oligomers. Several types of PML bodies have been observed. PML bodies can form hollow spheres that can sequester target proteins inside. Interacts (via SUMO-binding motif) with sumoylated proteins. Interacts (via C-terminus) with p53/TP53. Recruits p53/TP53 and CHEK2 into PML bodies, which promotes p53/TP53 phosphorylation at 'Ser-20' and prevents its proteasomal degradation. Interacts with MDM2, and sequesters MDM2 in the nucleolus, thereby preventing ubiquitination of p53/TP53. Interaction with PML-RARA oncoprotein and certain viral proteins causes disassembly of PML bodies and abolishes the normal PML function. Interacts with TERT, SIRT1, TOPBP1, TRIM27 and TRIM69. Interacts with ELF4 (via C-terminus). Interacts with Lassa virus Z protein and rabies virus phosphoprotein. Interacts (in the cytoplasm) with TGFBR1, TGFBR2 and PKM. Interacts (via the coiled-coil domain and when sumoylated) with SATB1. Interacts with UBE2I; the interaction is enhanced by arsenic binding. Interacts with SMAD2, SMAD3, DAXX, RPL11, HIPK2 and MTOR. Interacts with ITPR3, PPP1A and RB1. Interacts with RNF4, NLRP3, MAGEA2, RBL2, PER2, E2F4 and MAPK7/BMK1. Interacts with CSNK2A1 and CSNK2A3. Interacts with ANKRD2; the interaction is direct. Interacts with PPARGC1A AND KAT2A. Interacts (via SUMO-interacting motif) with sumoylated MORC3 (By similarity). Interacts with TRIM16. Interacts with PRDM1 (By similarity). Detected in the nucleolus after DNA damage. Acetylation at Lys-497 is essential for its nuclear localization. Within the nucleus, most of PML is expressed in the diffuse nuclear fraction of the nucleoplasm and only a small fraction is found in the matrix-associated nuclear bodies (PML-NBs). The transfer of PML from the nucleoplasm to PML-NBs depends on its phosphorylation and sumoylation. The B1 box and the RING finger are also required for the localization in PML-NBs. Also found in specific membrane structures termed mitochondria-associated membranes (MAMs) which connect the endoplasmic reticulum (ER) and the mitochondria (By similarity). The coiled-coil domain mediates a strong homo/multidimerization activity essential for core assembly of PML-NBs. Binds arsenic via the RING-type zinc finger. The Sumo interaction motif (SIM) is required for efficient ubiquitination, recruitment of proteasome components within PML-NBs and PML degradation in response to arsenic trioxide. Ubiquitinated; mediated by RNF4, RNF111, UHRF1, UBE3A/E6AP, BCR(KLHL20) E3 ubiquitin ligase complex, SIAH1 or SIAH2 and leading to subsequent proteasomal degradation. 'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination by RNF4 is polysumoylation-dependent (By similarity). Ubiquitination by RNF111 is polysumoylation-dependent (PubMed:23530056). Ubiquitination by BCR(KLHL20) E3 ubiquitin ligase complex requires CDK1/2-mediated phosphorylation at Ser-528 which in turn is recognized by prolyl-isopeptidase PIN1 and PIN1-catalyzed isomerization further potentiates PML interaction with KLHL20 (By similarity). Sumoylation regulates PML's: stability in response to extracellular or intracellular stimuli, transcription directly and indirectly, through sequestration of or dissociation of the transcription factors from PML-NBs, ability to regulate apoptosis and its anti-viral activities. It is also essential for: maintaining proper PML nuclear bodies (PML-NBs) structure and normal function, recruitment of components of PML-NBs, the turnover and retention of PML in PML-NBs and the integrity of PML-NBs. Undergoes 'Lys-11'-linked sumoylation. Sumoylation on all three sites (Lys-70, Lys-165 and Lys-500) is required for nuclear body formation. Sumoylation on Lys-165 is a prerequisite for sumoylation on Lys-70. Lys-70 and Lys-165 are sumoylated by PISA1 and PIAS2. PIAS1-mediated sumoylation of PML promotes its interaction with CSNK2A1/CK2 and phosphorylation at Ser-575 which in turn triggers its ubiquitin-mediated degradation. Sumoylation at Lys-500 by RANBP2 is essential for the proper assembly of PML-NBs. Desumoylated by SENP1, SENP2, SENP3, SENP5 and SENP6 (By similarity). Phosphorylation is a major regulatory mechanism that controls PML protein abundance and the number and size of PML nuclear bodies (PML-NBs). Phosphorylated in response to DNA damage, probably by ATR. HIPK2-mediated phosphorylation at Ser-17, Ser-45 and Ser-47 leads to increased accumulation of PML protein and its sumoylation and is required for the maximal pro-apoptotic activity of PML after DNA damage. MAPK1- mediated phosphorylations at Ser-404, Ser-515 and Ser-540 and CDK1/2-mediated phosphorylation at Ser-528 promote PIN1-dependent PML degradation. CK2-mediated phosphorylation at Ser-575 primes PML ubiquitination via an unidentified ubiquitin ligase (By similarity). Acetylation at Lys-497 is essential for its nuclear localization. Deacetylated at Lys-497 by SIRT1 and this deacetylation promotes PML control of PER2 nuclear localization (By similarity). Mice are born at the expected Mendelian rate and are fertile. They show leukopenia with reduced levels of circulating granulocytes and myeloid cells. They are highly susceptible to infections, causing a reduced life span. Mice do not exhibit normal apoptosis of hematopoietic stem cells after DNA damage due to irradiation. They do not exhibit normal apoptosis in response to FAS, TNF, TGFB1, interferons and ceramide, and show impaired activation of caspases in response to pro-apoptotic stimuli. Mice are highly susceptible to chemical carcinogens. Mice display accelerated revascularization after ischemia. Newborns have smaller brains with a reduced size of the brain cortex. Mice display aberrant learning and memory, lower levels of anxiety-like behavior and specific deficits in long-term plasticity. Mice display a compromised endogenous circadian clock with reduced precision and stability of the period length. Truncated N-terminus.