CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN;
DNA BINDING PROTEIN;
DNA BINDING PROTEIN, CYCLIC AMP RESPONSIVE;
DNA BINDING PROTEINS;
TRANSCRIPTION FACTOR;
Cyclic-AMP-responsive Transcriptional Activation of CREB-327 Involves Interdependent Phosphorylated Subdomains
of outstanding interest, This paper describes mutational analysis of CREB-327 (lacking the α domain), showing the importance of the α2 region and the DLSSD (Asp140-Leu-Ser-Ser-Asp144)-containing region that flank the PKA phosphoacceptor serine. Together with the results presented in [9], a strong argument can be made that the 50 or so amino acids around the phosphoacceptor serine are critical for basal and PKA-induced CREB activity. Data are also presented that suggest phosphorylation of residues in the α2 region is influenced by phosphorylation at the PKA phosphoacceptor site.
Characterization of Motis which are Critical for Activity of the Cyclic AMP-responsive Transcription Factor CREB
of outstanding interest, The authors present detailed mutational analysis of the kinase-inducible-domain region, with emphasis on the DLSSD (Asp140-Leu-Ser-Ser-Aspr44) motif, demonstrating the importance of sequences flanking Ser133 for CREB activity. The glutamine-rich amino-terminal Q1 region is also shown to play a role in CREB function. Partial-proteolysis experiments suggest that there is a structural difference between non-phosphorylated and Ser133-phosphorylated CREB, lending weight to the model that CREB is activated by phosphorylation through an allosteric mechanism.
The cAMP-regulated Enhancer-binding Protein ATF-1 Activates Transcription in Response to cAMP-dependent Protein Kinase A
of special interest, This report describes a new member of the ATF/CREB family capable of mediating cAMP-dependent induction of transcription. Conserved regions between ATF-1 and CREB correlate well with the regions that are found by CREB mutational analysis to be important for transcriptional activation. The lack of most of the Q1 region in ATF-1 suggests, however, that the function of this region is more complex than originally envisaged.
Cross-family Dimerization of Transcription Factors Fos/Jun and ATF/CREB Alters DNA-binding Specificity
of special interest, The authors present evidence showing that members of the ATF family, except for ATF-1, can form selective heterodimers with members of the Fos/Jun family. These cross-family heterodimers display different DNA-binding characteristics as compared with the homodimers, and often show a preference for binding CRE sequences.
Identification of Multiple Nuclear Factors that Interact with Cyclic Adenosine 3′, 5′-monophosphate Response Element-binding Protein and Activating Transcription Factor-2 by Protein-Protein Interactions
The Cellular Transcription Factor CREB Corresponds to Activating Transcription Factor 47 (ATF-47) and Forms Complexes with a Group of Polypeptides Related to ATF-43
CREM Gene: Use of Alternative DNA-binding Domains Generates Multiple Antagonists of cAMP-induced Transcription
of outstanding interest, This report describes what appears to be a negative regulator of cAMP-induced transcription, suggesting a mechanism for the attenuation of cAMP-inducible gene transcription observed even in the presence of stimulators of protein kinase A. Cell-specific splicing and expression of CREM suggests that its ability to modulate cAMP-dependent transcription may be finely tuned to specific situations as opposed to its being a universal antagonist. A major question remains as to whether CREM always functions as a transcriptional repressor given that CREM contains a kinase-inducible-domain-like region very similar to that occurring in CREB.
Transcriptional Antagonist cAMP-responsive Element Modulator (CREM) Down Regulates c-fos cAMP-induced Expression
of special interest, The authors show that down-regulation of c-fos expression after stimulation by serum or cAMP occurs by different mechanisms. CREM is only able to down-regulate cAMP-stimulated c-fos expression, while Fos down-regulates only serum-induced expression. Expression of anti-sense CREM RNA increases basal and cAMP-induced c-fos transcription.
2+/calmodulin- as Well as cAMP-dependent Protein Kinase
of special interest, This paper supports the findings of Sheng et al. [20]by showing that the phosphorylation of CREB by CAM kinase increases CRE-containing c-fos-promoter-driven transcription in vitro. The authors also present a model that demonstrates the possible role of CREB in associative learning.
The ATF/CREB Transcription Factor-binding Site in the Polymerase β Promoter Mediates the Positive Effect of N-methyl-N-nitro-N-nitrosoguanidine on Transcription
of special interest, This paper is interesting because it suggests that a phosphorylated CRE-binding protein is involved in mediating transcriptional regulation in response to DNA damage. Future analysis of the factor involved (possibly CREB), and how it may be modified, will help elucidate whether some of the signal transduction pathways proposed to modulate CREB activity (for example, those involving casein kinases) are physiologically significant.
Somatotroph Hypoplasia and Dwarfism in Transgenic Mice Expressing a Non-phosphorylatable CREB Mutant
of outstanding interest, This paper describes the use of an ectopically-expressed CREB mutant gene to disrupt a cellular developmental pathway. Pituitary somatotroph cells will normally proliferate in response to cAMP, but proliferation is blocked when the cells express a CREB gene mutated at Ser133. Although the mechanism by which the mutant CREB functions in somatotrophs is unclear, its ability to block cell proliferation does not appear to be due to a general toxic effect, as other cell types are able to express the gene.
