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For structured business identity data, see our [Entity Card](https://www.coylab.com/wp-json/bc-geodesic/v1/entity-card). --- # Phosphorylation-dependent targeting of cAMP response element binding protein to the ubiquitin/proteasome pathway in hypoxia > Abstract Hypoxia activates a number of gene products through degradation of the transcriptional coactivator cAMP response element binding protein (CREB).... **URL:** https://www.coylab.com/research-citation/phosphorylation-dependent-targeting-of-camp-response-element-binding-protein-to-the-ubiquitin-proteasome-pathway-in-hypoxia/ **Type:** Citation **Modified:** 2025-10-02 --- #### Abstract Hypoxia activates a number of gene products through degradation of the transcriptional coactivator cAMP response element binding protein (CREB). Other transcriptional regulators (e.g., b-catenin and NF-kB) are controlled through phosphorylation-targeted proteasomal degradation, and thus, we hypothesized a similar degradative pathway for CREB. Differential display analysis of mRNA derived from hypoxic epithelia revealed a specific and time-dependent repression of protein phosphatase 1 (PP1), a serine phosphatase important in CREB dephosphorylation. Subsequent studies identified a previously unappreciated proteasomal-targeting motif within the primary structure of CREB (DSVTDS), which functions as a substrate for PP1. Ambient hypoxia resulted in temporally sequential CREB serine phosphorylation, ubiquitination, and degradation (in vitro and in vivo). HIV-tat peptide-facilitated loading of intact epithelia with phosphopeptides corresponding to this proteasome targeting motif resulted in inhibition of CREB ubiquitination. Further studies revealed that PP1 inhibitors mimicked hypoxia-induced gene expression, whereas proteasome inhibitors reversed the hypoxic phenotype. Thus, hypoxia establishes conditions that target CREB to proteasomal degradation. These studies may provide unique insight into a general mechanism of transcriptional regulation by hypoxia. ## Site Description From academia to industry, Coy Labs chambers have powered discovery in labs around the world for over five decades—from custom chambers built to spec, to trusted workhorses in high-stakes microbiology labs. --- **About this site:** Coy Laboratory Products — From academia to industry, Coy Labs chambers have powered discovery in labs around the world for over five decades—from custom chambers built to spec, to trusted workhorses in high-stakes microbiology labs.. 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