Anti-PML Protein Antibody Picoband® Fluoro647 Conjugated

The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This phosphoprotein localizes to nuclear bodies where it functions as a transcription factor and tumor suppressor. Its expression is cell-cycle related and it regulates the p53 response to oncogenic signals. The gene is often involved in the translocation with the retinoic acid receptor alpha gene associated with acute promyelocytic leukemia (APL) . Extensive alternative splicing of this gene results in several variations of the protein's central and C-terminal regions; all variants encode the same N-terminus. Alternatively spliced transcript variants encoding different isoforms have been identified.

Cancer, Cancer Metabolism, Domain Families, Epigenetics and Nuclear Signaling, Metabolism, Metabolism Processes, Pathways and Processes, Response To Hypoxia, Transcription, Transcription Factors, Zinc Finger

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) . .

1. Dyck, J. A., Maul, G. G., Miller, W. H., Jr., Chen, J. D., Kakizuka, A., Evans, R. M. A novel macromolecular structure is a target of the promyelocyte-retinoic acid receptor oncoprotein. Cell 76: 333-343, 1994. 2. Giorgi, C., Ito, K., Lin, H.-K., Santangelo, C., Wieckowski, M. R., Lebiedzinska, M., Bononi, A., Bonora, M., Duszynski, J., Bernardi, R., Rizzuto, R., Tacchetti, C., Pinton, P., Pandolfi, P. P. PML regulates apoptosis at endoplasmic reticulum by modulating calcium release. Science 330: 1247-1251, 2010.

Nucleus . Nucleus, nucleoplasm. Cytoplasm. Nucleus, PML body. Nucleus, nucleolus . Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side. Early endosome membrane ; Peripheral membrane protein ; Cytoplasmic side . 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) . .