Disease relevance of CrebB-17A

• Our findings, along with the regulation of human Fascin1 (OMIM 602689) by CREB (cAMP response element-binding protein) binding protein, suggest FSCN1 as a candidate gene for developmental brain disorders [1].

Psychiatry related information on CrebB-17A

• The CREB family of proteins are critical mediators of gene expression in response to extracellular signals and are essential regulators of adaptive behavior and long-term memory formation [2].
• The effects of overexpressed dCREB2-b were not due to elevated locomotor activities of heat-shocked females nor due to more vigorous courtship behavior of paired wild-type males [3].
• Evidence from Aplysia, Drosophila, mice, and rats shows that CREB-dependent transcription is required for the cellular events underlying long-term but not short-term memory [4].
• CONCLUSIONS: Previous findings and results presented here demonstrate that CREB mutant mice have profound long-term memory deficits [5].
• Remarkably, this effect of CREB function is not restricted to simple conditioning tasks, but also affects complex behaviours such as spatial memory and memory for socially transmitted food preferences [5].

High impact information on CrebB-17A

• Using an inducible transgene that expresses a dominant negative member of the fly CREB family, LTM was specifically and completely blocked only after induction, while ARM and learning were unaffected [6].
• These results suggest that LTM formation requires de novo gene expression probably mediated by CREB family genes [6].
• Increases in the concentration of either calcium or cAMP can trigger the phosphorylation and activation of CREB [4].
• To understand the molecular regulation of sleep-like rest, we investigated the involvement of a candidate gene, cAMP response-element binding protein (CREB) [7].
• A non-circadian role for cAMP signaling and CREB activity in Drosophila rest homeostasis [7].

Biological context of CrebB-17A

• Thus, unlike the mammalian protein, the primary regulation of dCREB2 may occur at a different step from serine 231 phosphorylation [8].
• In vertebrates, the best characterized nuclear targets of PKA are the 'cAMP response element' (CRE) binding proteins (CREB) [9].
• We report the role of dCREB2, the Drosophila homolog of CREB/CREM, in circadian rhythms. dCREB2 activity cycles with a 24 hr rhythm in flies, both in a light:dark cycle and in constant darkness [10].
• Involvement of CREB both in LTM and circadian rhythm raises the possibility that per also plays a role in LTM [11].
• Together, these findings implicate CREB/ATF proteins in essential functions during molting and metamorphosis [12].

Anatomical context of CrebB-17A

• In this context, we have now investigated the presence of different dCREB transcripts in a stable, embryonic insect cell line, i.e., Drosophila Schneider 2 (S2) cells [9].
• In contrast, CREB expression has been less well characterized in testis germ cells [13].
• In the pineal of birds, Drosophila, and algae, cAMP/PKA pathway is functional in the output, but in mammalian suprachiasmatic nucleus (SCN), this pathway including the CREB/c-fos pathway, is believed to function in the input pathway [14].
• Moreover, we also show that synaptic output of larval mushroom body neurons is required for retrieval but not for acquisition and retention of the larval memory, including the CREB-dependent component [15].
• Studies at the larval neuromuscular junction, however, reveal a role for Adf1 in the modulation of synaptic growth-in contrast to the role established for dCREB2 in the control of synaptic function (Davis et al., 1996) [16].

Associations of CrebB-17A with chemical compounds

• We have characterized a Drosophila gene that is a highly conserved homolog of the mammalian cyclic AMP (cAMP)-responsive transcription factors CREB and CREM [17].
• Here we present genetic and pharmacological evidence in Drosophila suggesting that repetitive exposures to nicotine induce a hyper-responsiveness through synthesis of new protein(s) via CREB-mediated gene transcription [18].
• The mammalian CREB protein consists of an amino-terminal transcriptional activation domain and a carboxy-terminal DNA-binding domain comprised of a basic region and a leucine zipper [19].
• A mutation in the Drosophila homolog of CREB, dCREB2, enhances lethality due to polyglutamine peptides (polyQ), and an additional copy of dCREB2 partially rescues this lethality [20].
• Helicon Therapeutics has been formed to identify drug compounds that enhance memory formation via augmentation of CREB biochemistry [21].

Other interactions of CrebB-17A

• Intriguingly, larval memory produced by the appetitive conditioning lasts medium term and depends on both amnesiac and cAMP response element-binding protein (CREB) [15].
• We propose that dCREB2 supports cycling of the Period/Timeless oscillator [10].
• In contrast, the dCREB-B and mammalian CREB zipper domains differ considerably from the dCREB-A zipper in both length and composition [19].
• This protein, dCREB-B, contains 285 amino acids and is remarkably similar within the basic/zipper region to the corresponding portion of mammalian CREB [19].

Analytical, diagnostic and therapeutic context of CrebB-17A

• Northern blot analysis shows that multiple transcripts of the dCREB-B gene are expressed in embryonic and adult tissues and that these transcripts arise from both strands of the DNA.(ABSTRACT TRUNCATED AT 250 WORDS)[19]
• In aplysia, CREB activation has been interfered with by microinjection of CRE containing oligonucleotides into cultured neurons [22].
• Genetic dissection of structural and functional components of synaptic plasticity. III. CREB is necessary for presynaptic functional plasticity [23].
• Sequence analysis of the 5'-flanking region of the gene revealed a high GC content, six CCGCCC Sp-1-binding motifs, CREB, LBP-1 (leader-binding protein 1), and TGGCA-binding consensus sites [24].
• We have previously described the cloning of a cyclic AMP response-element (CRE)-binding protein, dCREB-A, in Drosophila melanogaster that is similar to the mammalian CRE-binding protein CREB. dCREB-A is a member of the bZIP family of transcription factors, shows specific binding to the (CRE), and can activate transcription in cell culture [25].

References