PML

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For Research Use Only. Not For Clinical Use.


Background

Regulates RB1 phosphorylation and activity. Required for normal development of the brain cortex during embryogenesis. Can sequester herpes virus and varicella virus proteins inside PML bodies, and thereby inhibit the formation of infectious viral particles. Regulates phosphorylation of ITPR3 and plays a role in the regulation of calcium homeostasis at the endoplasmic reticulum (By similarity). Regulates transcription activity of ELF4. 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. Isoform PML-4 has a multifaceted role in the regulation of apoptosis and growth suppression: activates RB1 and inhibits AKT1 via interactions with PP1 and PP2A phosphatases respectively, negatively affects the PI3K pathway by inhibiting MTOR and activating PTEN, and positively regulates p53/TP53 by acting at different levels (by promoting its acetylation and phosphorylation and by inhibiting its MDM2-dependent degradation). Isoform PML-4 also: acts as a transcriptional repressor of TBX2 during cellular senescence and the repression is dependent on a functional RBL2/E2F4 repressor complex, regulates double-strand break repair in gamma-irradiation-induced DNA damage responses via its interaction with WRN, acts as a negative regulator of telomerase by interacting with TERT, and regulates PER2 nuclear localization and circadian function. Isoform PML-6 inhibits specifically the activity of the tetrameric form of PKM. The nuclear isoforms (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4 and isoform PML-5) in concert with SATB1 are involved in local chromatin-loop remodeling and gene expression regulation at the MHC-I locus. Isoform PML-2 is required for efficient IFN-gamma induced MHC II gene transcription via regulation of CIITA. Cytoplasmic PML is involved in the regulation of the TGF-beta signaling pathway. PML also regulates transcription activity of ELF4 and can act as an important mediator for TNF-alpha- and IFN-alpha-mediated inhibition of endothelial cell network formation and migration.
Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins

Predicted location

Intracellular

Single cell type specificity

Cell type enhanced (Adipocytes)

Immune cell specificity

Low immune cell specificity

Cell line specificity

Low cell line specificity

Interaction

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 HIPK2, TERT, SIRT1, TOPBP1, TRIM27 and TRIM69. Interacts with ELF4 (via C-terminus). Interacts with ITPR3. 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 (PML-RARA oncoprotein, via the coiled-coil domain) with UBE2I; the interaction is enhanced by arsenic binding and is required for PML-RARA oncoprotein sumoylation and inhibition of RARA transactivational activity. Interacts with RB1, PPP1A, SMAD2, SMAD3, DAXX, RPL11 and MTOR. Interacts with PPARGC1A and KAT2A. Interacts with CSNK2A1 and CSNK2A3. Interacts with ANKRD2; the interaction is direct. Interacts (via SUMO-interacting motif) with sumoylated MORC3 (PubMed:20501696). Isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4, isoform PML-5 and isoform PML-6 interact with RNF4. Isoform PML-1 interacts with NLRP3. Isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4 and isoform PML-5 interact with MAGEA2, RBL2, PER2 and E2F4. Isoform PML-2 interacts with CIITA. Isoform PML-2, isoform PML-3 and isoform PML-4 interact with TBX2. Isoform PML-4 interacts with RANBP2, HDAC7, KAT6A, WRN, PIN1, TBX3 and phosphorylated MAPK1/ERK2. Isoform PML-4 interacts with the CTNNB1 and TCF7L2/TCF4 complex. Isoform PML-4 preferentially interacts with MAPK7/BMK1 although other isoforms (isoform PML-1, isoform PML-2, isoform PML-3 and isoform PML-6) also interact with it. Isoform PML-12 interacts with PIAS1, PIAS2 (isoform PIAS2-alpha) and CSNK2A1/CK2. Interacts with TRIM16. Interacts with PRDM1/Blimp-1 (PubMed:28842558). (Microbial infection) Interacts with Lassa virus Z protein and rabies virus phosphoprotein. (Microbial infection) Isoform PML-1 interacts with herpes simplex virus-1/HHV-1 ICP0. (Microbial infection) Isoform PML-2 interacts with human adenovirus 2 E1A and this interaction stimulates E1A-dependent transcriptional activation. (Microbial infection) Isoform PML-4 interacts with VZV capsid protein VP26/ORF23 capsid protein. (Microbial infection) The sumoylated isoform PML-4 interacts with encephalomyocarditis virus (EMCV) RNA-directed RNA polymerase 3D-POL (P3D-POL). (Microbial infection) Isoform PML-6 interacts with moloney murine leukemia virus (MoMLV) integrase (IN) and reverse transcriptase (RT). (Microbial infection) Isoform PML-4 and isoform PML-5 interact with human adenovirus 5 E1B-55K protein; these interactions promote efficient subnuclear targeting of E1B-55K to PML nuclear bodies. (Microbial infection) Isoform PML-3 interacts (via RING-type zinc finger) with human foamy virus bel1/tas and bet. (Microbial infection) Interacts with human cytomegalovirus (HHV-5) immediate early protein IE1; this interaction mediates PML desumoylation and PML-mediated sumoylation of IE1.

Molecular function

Activator, DNA-binding, Transferase

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