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Related Concept Videos

Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
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Regulation of Expression at Multiple Steps01:23

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Constitutive and Regulated Gene Expression01:27

Constitutive and Regulated Gene Expression

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Gene expression in prokaryotes is governed by constitutive and regulated systems, allowing cells to balance the production of essential proteins with adaptive responses to environmental changes.Constitutive Gene ExpressionConstitutive, or housekeeping, genes are continuously expressed as they encode proteins vital for fundamental cellular processes. These include enzymes for glycolysis, ribosomal components for protein synthesis, and proteins involved in DNA replication. Their constant...
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Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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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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Related Experiment Video

Updated: Feb 11, 2026

Generation of Alpha-Synuclein Preformed Fibrils from Monomers and Use In Vivo
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p27Kip1 regulates alpha-synuclein expression.

Edurne Gallastegui1, Carla Domuro1, Joan Serratosa2

  • 1Department of Biomedical Sciences, (CIBERONC), University of Barcelona, Barcelona, Spain.

Oncotarget
|April 18, 2018
PubMed
Summary
This summary is machine-generated.

Cell cycle regulators p27 and p21 suppress alpha-synuclein (α-SYN) transcription. This finding reveals a new mechanism controlling α-SYN levels, potentially impacting neurodegenerative diseases like Parkinson's.

Keywords:
E2F4alpha synucleinp21Cip1p27Kip1transcription

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Alpha-synuclein (α-SYN) aggregation is central to synucleinopathies.
  • Transcriptional regulation of α-SYN remains poorly understood.

Purpose of the Study:

  • Investigate the role of p27Kip1 (p27) in regulating α-SYN expression.
  • Elucidate the molecular mechanisms underlying α-SYN transcriptional control.

Main Methods:

  • CRISPR/Cas9 gene editing to delete p27 in neural cells.
  • p21Cip1 (p21) knockdown experiments.
  • Chromatin immunoprecipitation (ChIP) assays.
  • Luciferase reporter assays.

Main Results:

  • Selective deletion of p27 increased α-SYN levels.
  • p21 knockdown also elevated α-SYN levels, indicating collaborative repression.
  • Repression involves transcription factor E2F4 and p130, dependent on Cdk activity.
  • ChIP and luciferase assays confirmed direct binding and transcriptional regulation of the α-SYN gene by p27, p21, and E2F4.

Conclusions:

  • p27 and p21 act as negative regulators of α-SYN transcription.
  • This pathway, involving E2F4/p130 and Cdk activity, offers a novel mechanism for controlling α-SYN expression.
  • Cell cycle regulators may play a significant role in the pathogenesis of synucleinopathies.