POLR2L Activators

POLR2L can initiate a series of intracellular events that lead to its activation. Compounds such as A23187 and Ionomycin function as calcium ionophores, which facilitate the influx of calcium ions into the cell. The increased intracellular calcium concentration can have a direct effect on enzymes and proteins that require calcium ions for their activity. Since POLR2L is a subunit of RNA polymerase II, which requires calcium for optimal function, these ionophores can enhance POLR2L's role in the transcription process. Phorbol 12-myristate 13-acetate (PMA), on the other hand, activates protein kinase C (PKC), which is known to phosphorylate the C-terminal domain (CTD) of RNA polymerase II. This phosphorylation event is crucial for the initiation and elongation phases of transcription, thus activating POLR2L. Forskolin acts by a different mechanism, stimulating adenylate cyclase, resulting in elevated levels of cyclic AMP (cAMP). The rise in cAMP activates protein kinase A (PKA), which then can phosphorylate and activate transcription factors that work cooperatively with POLR2L as part of the RNA polymerase II complex.

Inhibitors of protein phosphatases, such as Okadaic acid, Cantharidin, and Calyculin A, maintain POLR2L in an activated state by preventing the dephosphorylation of the RNA polymerase II CTD. The persistent phosphorylation of the CTD keeps POLR2L active and engaged in the transcription elongation process. Brefeldin A indirectly affects POLR2L through the disruption of the Golgi apparatus, leading to cellular stress responses that may enhance transcriptional activity. MG-132's role is to inhibit the proteasome, which prevents the degradation of proteins that regulate the activity of RNA polymerase II, thereby supporting POLR2L's activation. The action of histone deacetylase inhibitors, such as Trichostatin A and Sodium butyrate, is to facilitate a more relaxed chromatin structure by increasing the acetylation of histones. This relaxed structure allows POLR2L as part of the RNA polymerase II complex better access to DNA for transcription. Lastly, 5-Azacytidine, by being incorporated into RNA and DNA, leads to changes in the methylation pattern of DNA, which can alter gene expression profiles and indirectly modify the activity of POLR2L through the complex transcriptional machinery.