Promyelocytic leukemia protein (PML) (PML)

The Promyelocytic leukemia protein (PML) is a tumor suppressor and the primary structural component of PML nuclear bodies (PML-NBs), which are subnuclear organelles involved in various cellular processes (UniProt P29590). PML functions as a scaffold, recruiting numerous proteins to regulate apoptosis, cellular senescence, DNA damage repair, and antiviral responses (PubMed: 25324444). In Acute Promyelocytic Leukemia (APL), a chromosomal translocation typically fuses the PML gene with the Retinoic Acid Receptor Alpha (RARA) gene, creating the PML-RARA oncoprotein that disrupts normal PML-NB formation (NIH: NBK1404). Therapeutic agents like arsenic trioxide directly target the PML moiety of both the fusion protein and the wild-type protein, inducing their degradation and restoring cellular differentiation (Science, 2010, 328(5975):240-243). Beyond APL, wild-type PML is increasingly recognized for its role in solid tumors and as a potential target in viral infections and other malignancies (Nature Reviews Cancer, 2011, 11(11):797-811). The protein contains a tripartite motif (TRIM) consisting of a RING finger, two B-box zinc fingers, and a coiled-coil domain, which are essential for its multimerization and function (PubMed: 10644755). Loss of wild-type PML expression is observed in many human cancers, correlating with poor prognosis and tumor progression (PubMed: 15064413). Research continues to explore the therapeutic potential of modulating wild-type PML levels in non-APL contexts to exploit its tumor-suppressive properties.

Other names

TRIM19Tripartite motif-containing protein 19MYLRNF71Protein P8675

Arsenic trioxide binds directly to the cysteine residues within the zinc fingers of the PML B2 domain, which triggers the recruitment of SUMO-conjugating enzymes, leading to hyper-SUMOylation of the protein. This modification facilitates the recruitment of the E3 ubiquitin ligase RNF4, resulting in the polyubiquitination and subsequent proteasomal degradation of the PML protein (Science, 2010, 328(5975):240-243; PubMed: 18408710).