Retinoblastoma
The retinoblastoma families of proteins are key cell cycle regulatory molecules important for the differentiation of various mammalian cell types. The retinoblastoma protein (RB) regulates transcription of a variety of genes either by blocking the activation domain of various activators or by active repression (finding of appropriate promoters). If the RB?s function is lost, it will lead to a variety of cancers and defects in the development of certain cell types. Phosphorylation of RB by cyclin and cyclin-dependent kinases leads to dissociation of RB from E2F (protein receptor), allowing progression into the S-phase. RB has also been proven to have the ability to block cell cycle progression from G1- to the S-phase. (Chan et al, 2001)RB is also a general tumor suppressor, which is associated with a central N (A/B) and C-terminal (pocket domains, which are binding sites for RB) that were defined to have the ability to bind cellular and viral proteins that affect the cell division cycle. Mutations in the pocket domain region are often tumorigenic. These pocket domains are also present in homologues structures of RB that exhibit similar protein binding and functional characteristics pertaining to the cell division cycle. Even
In a ligand-dependent gene expression mediated by GRs, it binds as a homodimer to the glucocorticoid response element (GRE) and accelerates transcription initiation at the promoter of the target genes. GR?s various functions have led to the conclusion that the regulation of metabolic and developmental processes essential for survival is controlled by the GR. RB is also critical for the maximal activation of NR and GR. al, 2000)The functions of NR, GR, and AHR all deal with the N-terminal. The findings that AHR cooperates with RB via a direct interaction suggest an additional mechanism through which environmental signals can function to activate RB. These coactivators modify local chromatic structure by acetylating histone, which directly assembles the transcription-commencing complex. (Singh et al, 2001)Nuclear receptors (NRs) represent a super family of structurally and functionally related ligand-inducible transcription factors that deal with different biological events such as development, differentiation, and homeostasis. In a NR interaction RB is allowed to release from E2F allowing progression into the S-phase. Al, 2000)AHR, like RB is also responsive to environmental signal that inhibit cell cycle progression by commencing the dephosphorylation of RB. In a GR interaction, the repression of E2F activity and cell growth requires another pocket domain, hBRM (binding protein). though these structures bind to other proteins and have conspicuous molecular and cellular characteristics, they both have the ability to restrain cell growth by inhibiting the pocket domain-binding E2F family of transcription factors. This binding protein is part of a multisubunit human SWI/SNF complexes (Proteins that function in the reorganization of chromatin structure and influence the activity of proteins by affecting their access to regulatory sites).
Common topics in this essay:
A/B C-terminal,
LBD Ligand-dependent,
RB AHR,
AHR RB,
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S-phase GR,
GR AHR,
N-terminal A/B,
NR GR-,
S-phase Chan,
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cell cycle,
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puga et al,
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cycle progression,
rb critical,
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singh et,
cell division cycle,
division cycle,
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