Sandbox 7465: Difference between revisions
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'''FIGURE:''' | '''FIGURE:''' | ||
This is a crystal structure of FosB from ''Staphylococcus aureus'' This is a similar structure to DeltaFosB, although it retains 2 destabilizing elements which are spliced in the DeltaFosB variant.The DeltaFosB transcription factor should include 3 domains | This is a crystal structure of FosB from ''Staphylococcus aureus'' This is a similar structure to DeltaFosB, although it retains 2 destabilizing elements which are spliced in the DeltaFosB variant. The DeltaFosB transcription factor should include 3 domains: a transactivating domain, a DNA binding domain, and a signal sensing domain. DeltaFosB includes is a basic motif, a Leucine zipper, and a bZIP domain scene | ||
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The transcriptional factor DeltaFosB is unique in that it is a more stable form of FosB. There are two proposed regions that are cause for FosB’s instability; The amino acid sequences 278-337 and 278-337 contribute to proteasome-dependent FosB degradation. Proteins which undergo degradation are typically targeted by polyubiquitylation. HA-ubiquitin has been detected in FosB immunoprecipitations, but not in DeltaFosB, which is consistent with findings that DeltaFosB is formed through proteasomal degradation of FosB (Carle et al., 2007). | The transcriptional factor DeltaFosB is unique in that it is a more stable form of FosB. There are two proposed regions that are cause for FosB’s instability; The amino acid sequences 278-337 and 278-337 contribute to proteasome-dependent FosB degradation. Proteins which undergo degradation are typically targeted by polyubiquitylation. HA-ubiquitin has been detected in FosB immunoprecipitations, but not in DeltaFosB, which is consistent with findings that DeltaFosB is formed through proteasomal degradation of FosB (Carle et al., 2007). | ||
In general, Transcription Factors contain three domains, a Trans-Activating Domain, a DNA Binding Domain, and a Signal Sensing Domain. Three domains have been consistently noted on FosB. The first is a bZIP domain, located on amino acids 155-218. The second is a basic motif, located on amino acids 157-182, and the third is a leucine-zipper, located on amino acids 183-211. | In general, Transcription Factors contain three domains, a Trans-Activating Domain, a DNA Binding Domain, and a Signal Sensing Domain. Three domains have been consistently noted on FosB. (See Figure 1.)The first is a bZIP domain, located on amino acids 155-218. The second is a basic motif, located on amino acids 157-182, and the third is a leucine-zipper, located on amino acids 183-211. | ||
Alternative splicing removes two destabilizing elements from FosB, generating the more stable, longer-lived DeltaFosB possessing a half-life increased by 5 fold. A 140-nucleotide sequence is removed from exon 4 of the primary FosB transcript, resulting in a one-nucleotide frameshift and the formation of an early stop codon (TGA). This results in premature termination of DeltaFosB translation; therefore, proteins translated from DeltaFosB mRNA are missing several amino acids present at the C-terminal of full-length FosB proteins that normally destabilize the proteins. FosB contains a sequence of amino acids (278-337) that is normally targeted for degradation by proteasomes. The DeltaFosB variant lacks this sequence resulting in increased stability as it is not recognized and therefore not degraded by proteasomes. Another contributing factor to the stability of DeltaFosB is phosphorylation by protein kinases | Alternative splicing removes two destabilizing elements from FosB, generating the more stable, longer-lived DeltaFosB possessing a half-life increased by 5 fold. A 140-nucleotide sequence is removed from exon 4 of the primary FosB transcript, resulting in a one-nucleotide frameshift and the formation of an early stop codon (TGA). This results in premature termination of DeltaFosB translation; therefore, proteins translated from DeltaFosB mRNA are missing several amino acids present at the C-terminal of full-length FosB proteins that normally destabilize the proteins. FosB contains a sequence of amino acids (278-337) that is normally targeted for degradation by proteasomes. The DeltaFosB variant lacks this sequence resulting in increased stability as it is not recognized and therefore not degraded by proteasomes. Another contributing factor to the stability of DeltaFosB is phosphorylation by protein kinases | ||
