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Master Transcription Regulators02:23

Master Transcription Regulators

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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
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Transcriptional Regulation: Riboswitches01:23

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Riboswitches are RNA elements that regulate gene expression by altering their secondary structures in response to specific effector molecules. These elements, located in the leader regions of certain mRNAs, act as transcriptional regulators by toggling between alternative conformations to control downstream gene expression. Riboswitch-mediated regulation is a precise mechanism for modulating biosynthetic pathways, as exemplified by the riboflavin biosynthesis pathway in Bacillus...
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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes
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FBXW7 regulates a mitochondrial transcription program by modulating MITF.

Franco Abbate1,2,3, Brateil Badal1,2,3, Karen Mendelson1,2,3

  • 1Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.

Pigment Cell & Melanoma Research
|April 18, 2018
PubMed
Summary
This summary is machine-generated.

Loss of FBXW7 in melanoma promotes mitochondrial gene expression via MITF, leading to poor patient outcomes. This study reveals FBXW7 as a key regulator of melanoma

Keywords:
FBXW7MITFPGC-1alphamelanomametabolismmitochondria

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • FBXW7 acts as a tumor suppressor in various cancers, including melanoma.
  • The precise mechanisms underlying FBXW7's tumor-suppressive role in melanoma remain incompletely understood.

Purpose of the Study:

  • To elucidate the transcriptomic changes regulated by FBXW7 in melanoma.
  • To investigate the functional relationship between FBXW7, MITF, and mitochondrial metabolism in melanoma.

Main Methods:

  • RNA sequencing of human melanoma cell lines with FBXW7 silenced (n=10).
  • Analysis of a human melanoma tumor cohort (n=51).
  • In vitro studies assessing the impact of FBXW7 and MITF manipulation.

Main Results:

  • Loss of FBXW7 significantly enhances a mitochondrial gene transcriptional program in melanoma.
  • This FBXW7-regulated program is dependent on MITF (microphthalmia-associated transcription factor).
  • FBXW7 inactivation leads to elevated MITF protein levels and is an upstream regulator of the MITF/PGC-1 signaling pathway, correlating with poor patient prognosis.

Conclusions:

  • FBXW7 loss promotes a mitochondrial metabolic phenotype in melanoma through MITF.
  • Targeting FBXW7 or the MITF/PGC-1 pathway may offer therapeutic strategies for melanoma.
  • Understanding FBXW7's role is crucial for deciphering melanoma progression and identifying novel therapeutic targets.