Sandbox Reserved 973: Difference between revisions
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<Structure load='4F3L' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />' | <Structure load='4F3L' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' />' | ||
= 4F3L : CLOCK:BMAL1 heterodimeric complex = | |||
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On the other hand, CLOCK:BMAL 1 is also able to activate the transcription of retinoic acid-related nuclear receptors: Rev-erbα and Rorα.These proteins have the ability to regulate the transcription of Bmal1, RORα as an activator and REV-ERBα as a repressor. | On the other hand, CLOCK:BMAL 1 is also able to activate the transcription of retinoic acid-related nuclear receptors: Rev-erbα and Rorα.These proteins have the ability to regulate the transcription of Bmal1, RORα as an activator and REV-ERBα as a repressor. | ||
But this molecular clock is also regulated by post-translational modifications of the subunits, notably phosphorylation and ubiquitination. Some modifiers proteins can modify the stabibility or influence the translocation of some core clock actors, including BMAL1 and CLOCK. That's the case of 2 types of Casein kinase 1 (CK1). Mutations in these modifiers can shorten the circadian cycle of the mamals and cause serious sleep disorders. | But this molecular clock is also regulated by post-translational modifications of the subunits, notably phosphorylation and ubiquitination. Some modifiers proteins can modify the stabibility or influence the translocation of some core clock actors, including BMAL1 and CLOCK. That's the case of 2 types of Casein kinase 1 (CK1). Mutations in these modifiers can shorten the circadian cycle of the mamals and cause serious sleep disorders. | ||
NeveLrtheless recents studies showed that every cell has its autonomy towards the circadian cycle and it is important to notice that the two genes Clock and Bmal1 are not identically expressed in every tissues and that the two proteins don't act the same way in this different cell types. Clock mRNA follow a transcriptional cycle in the peripheric oscillators whereas it is constitutively expressed in the SCN. Futhermore the different ROR proteins which have feedback effects on Bmal1 transcription are expressed in a tissue-specific manner, so BMAL1 has various functions at various moments. Again CLOCK doesn't have the same influence on downstream regulated genes depending on the tissue. For example , CLOCK has a limited impact on the amplitudes of the Rev-erbα mRNA oscillation in the SCN. But Clock−/− mice show a important decrease of the same amplitude in the liver. Thus it is important to keep in mind that the CLOCK:BMAL1 complex subunits are expressed in tissue-specific patterns and that the heterodimer makes a tissue-specific regulation of the circadian clock,which drive the study of the complex functions very difficult. | |||
The two peptides involved in the dimere have very similar sequences . In ''mus musculus'' BMAL1 is 387 residues long and CLOCK is 361. | The two peptides involved in the dimere have very similar sequences . In ''mus musculus'' BMAL1 is 387 residues long and CLOCK is 361. | ||
