TFIIIC35 Activators

Chemical activators of TFIIIC35 can initiate a cascade of biochemical events leading to the protein's activation. Zinc chloride and magnesium chloride engage with TFIIIC35 by stabilizing its structure and the transcription complex it forms part of, ensuring proper folding and conformation. This stabilization is crucial as it aids in the maintenance of the protein's functionality during the initiation of RNA polymerase III transcription. Concurrently, sodium fluoride's inhibitory effect on serine/threonine phosphatases results in the upregulation of TFIIIC35's phosphorylation state, a modification that is indispensable for its activation. Likewise, potassium chloride contributes to this process by optimizing the ionic environment, which is essential for the structural integrity of TFIIIC35 and its interaction with other molecules involved in transcription.

Further activation of TFIIIC35 arises through the action of forskolin, ionomycin, and phorbol 12-myristate 13-acetate (PMA). Forskolin raises cAMP levels, indirectly causing the activation of protein kinase A, which then phosphorylates TFIIIC35. Ionomycin, by increasing intracellular calcium, can activate calcium-dependent kinases that may target TFIIIC35 for phosphorylation. PMA's role in the activation of protein kinase C leads to similar phosphorylative activation of TFIIIC35. AICAR triggers the activation of AMP-activated protein kinase, another enzyme that can phosphorylate and activate TFIIIC35. Conversely, calyculin A, cantharidin, and okadaic acid maintain TFIIIC35 in an active state by inhibiting protein phosphatases, thus preventing the dephosphorylation and subsequent inactivation of the protein. Lastly, anisomycin prompts the activation of stress-activated protein kinases which, in turn, can phosphorylate and activate TFIIIC35, enhancing its role in transcription initiation by RNA polymerase III. Each chemical, through its unique mechanism, ensures that TFIIIC35 is phosphorylated and consequently active, facilitating its critical role in gene expression.