{'fraction_non_alphanumeric': 0.026920551543007223, 'fraction_numerical': 0.019041365725541694, 'mean_word_length': 6.855670103092783, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Cyclic‐AMP‐responsive transcriptional activation of CREB‐327 involves interdependent phosphorylated subdomains.

Cyclic AMP‐regulated gene expression is mediated by specific phosphoproteins (CREBs) which bind to cAMP‐responsive elements of gene promoters. By analyzing the transactivation activities and phosphorylations in vivo of deletion and point mutated chimeric fusion proteins of the placental CREB‐327, in which the DNA‐binding domain is replaced by the heterologous binding‐domain of the yeast transcription factor GAL4, we localized the cAMP‐responsive and phosphorylated domain to a minimal‐essential sequence module of 46 amino acids (residues 92–137). This serine‐rich, multiply‐phosphorylated sequence consists of at least three interdependent subdomains required for transcriptional activation. Although phosphorylation of serine‐119 by cyclic AMP‐dependent protein kinase A is necessary for transcriptional activation, such activation requires both a phosphorylated heptadecapeptide domain located ten residues amino terminal to the serine‐119 and an eleven‐residue domain carboxyl terminal to the serine‐119. Deletion of these two domains does not impair phosphorylation of serine‐119. Further, deletion of the carboxyl‐terminal domain does not alter phosphorylation of the heptadecapeptide domain. We propose that akin to the phosphorylation‐dependent activation of enzymes, the transcriptional transactivation functions of CREB‐327 involve a phosphorylation‐dependent allosteric conformational mechanism.