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.
SEE ALSO...
| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
A23187 | 52665-69-7 | sc-3591 sc-3591B sc-3591A sc-3591C | 1 mg 5 mg 10 mg 25 mg | $55.00 $131.00 $203.00 $317.00 | 23 | |
A23187, also known as Calcimycin, is a calcium ionophore that increases intracellular calcium levels. Elevated intracellular calcium activates the protein POLR2L as it is a subunit of RNA polymerase II, which requires appropriate calcium levels for optimal conformation and function. | ||||||
PMA | 16561-29-8 | sc-3576 sc-3576A sc-3576B sc-3576C sc-3576D | 1 mg 5 mg 10 mg 25 mg 100 mg | $41.00 $132.00 $214.00 $500.00 $948.00 | 119 | |
This compound, commonly known as PMA, activates protein kinase C (PKC). PKC has been shown to phosphorylate the C-terminal domain (CTD) of RNA polymerase II, which includes the POLR2L subunit, leading to the activation of POLR2L as part of the polymerase complex. | ||||||
Ionomycin | 56092-82-1 | sc-3592 sc-3592A | 1 mg 5 mg | $78.00 $270.00 | 80 | |
Ionomycin is a calcium ionophore like A23187. It selectively binds to calcium and transports it across cell membranes, increasing intracellular calcium concentration. As with A23187, this increase in calcium can enhance the function of RNA polymerase II by affecting the POLR2L subunit, which is sensitive to changes in calcium levels for its activity. | ||||||
Okadaic Acid | 78111-17-8 | sc-3513 sc-3513A sc-3513B | 25 µg 100 µg 1 mg | $291.00 $530.00 $1800.00 | 78 | |
Okadaic acid is an inhibitor of protein phosphatases PP1 and PP2A. Inhibition of these phosphatases prevents dephosphorylation of the RNA polymerase II CTD, which contains the POLR2L subunit. Persistent phosphorylation of CTD is associated with active elongation phase of transcription, thereby maintaining POLR2L in an activated state. | ||||||
Cantharidin | 56-25-7 | sc-201321 sc-201321A | 25 mg 100 mg | $89.00 $279.00 | 6 | |
Cantharidin is another inhibitor of protein phosphatases PP1 and PP2A. By inhibiting these phosphatases, cantharidin causes an increase in the phosphorylation state of proteins, including the POLR2L subunit as part of the RNA polymerase II complex, leading to its activation and prolonged transcriptional activity. | ||||||
Calyculin A | 101932-71-2 | sc-24000 sc-24000A | 10 µg 100 µg | $163.00 $800.00 | 59 | |
Similar to okadaic acid and cantharidin, Calyculin A is an inhibitor of protein phosphatases PP1 and PP2A. By preventing dephosphorylation, Calyculin A maintains the phosphorylation of the CTD of RNA polymerase II, including the POLR2L subunit, which is essential for transcription elongation and hence constitutes an activation of POLR2L. | ||||||
Brefeldin A | 20350-15-6 | sc-200861C sc-200861 sc-200861A sc-200861B | 1 mg 5 mg 25 mg 100 mg | $31.00 $53.00 $124.00 $374.00 | 25 | |
Brefeldin A disrupts the structure and function of the Golgi apparatus, leading to a cascade of cellular responses that include alterations in signaling pathways. This disruption can indirectly lead to changes in transcription factor activity and the subsequent activation of RNA polymerase II, where POLR2L is a component, to compensate for the stress response. | ||||||
MG-132 [Z-Leu- Leu-Leu-CHO] | 133407-82-6 | sc-201270 sc-201270A sc-201270B | 5 mg 25 mg 100 mg | $60.00 $265.00 $1000.00 | 163 | |
MG-132 is a proteasome inhibitor. By inhibiting the degradation of transcriptional regulators and other proteins, MG-132 can indirectly increase the activity of RNA polymerase II, including the POLR2L subunit, by preventing the degradation of proteins that enhance RNA polymerase II activity or proteins that would normally suppress the dephosphorylation of its CTD. | ||||||
Trichostatin A | 58880-19-6 | sc-3511 sc-3511A sc-3511B sc-3511C sc-3511D | 1 mg 5 mg 10 mg 25 mg 50 mg | $152.00 $479.00 $632.00 $1223.00 $2132.00 | 33 | |
Trichostatin A is a histone deacetylase inhibitor. By changing the acetylation status of histones, it can result in a more relaxed chromatin structure, which facilitates transcription. This indirectly can increase the activity of the POLR2L-containing RNA polymerase II complex by allowing it greater access to DNA templates for transcription. | ||||||
Sodium Butyrate | 156-54-7 | sc-202341 sc-202341B sc-202341A sc-202341C | 250 mg 5 g 25 g 500 g | $31.00 $47.00 $84.00 $222.00 | 19 | |
Sodium butyrate, another histone deacetylase inhibitor, similarly to Trichostatin A, induces hyperacetylation of histones, enhancing transcription by RNA polymerase II where POLR2L is involved, by improving the accessibility of transcriptional machinery to DNA. | ||||||