Related Experiment Video

Updated: Jul 19, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

Multiple pathways regulate intracellular shuttling of MoKA, a co-activator of transcription factor KLF7

Silvia Smaldone1, Francesco Ramirez

  • 1Child Health Institute of New Jersey, Robert W. Johnson Medical School, 89 French Street, New Brunswick, NJ 08901, USA.

Nucleic Acids Research
|September 23, 2006
PubMed

Insights

MoKA protein regulates neuronal differentiation by interacting with KLF7. This study identifies specific sequences controlling MoKA

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Neuroscience

Background:

  • MoKA is a novel F-box protein that stimulates KLF7, a key regulator of neuronal differentiation.
  • MoKA's intracellular localization is predominantly cytosolic, suggesting the presence of nuclear localization signals (NLSs) and nuclear export signals (NESs).

Purpose of the Study:

  • To precisely identify and localize the functional sequences responsible for MoKA's intracellular transport and transcriptional activity.
  • To elucidate the mechanisms governing MoKA's shuttling between the nucleus and cytoplasm.

Main Methods:

  • Forced expression of MoKA-fusion proteins in mammalian cells.
  • Analysis of protein localization using microscopy.
  • Transcriptional activity assays employing the chimeric GAL4 system.

Main Results:

  • Only one of three putative NLSs is essential for MoKA nuclear import, interacting with karyopherin receptors.
  • Three distinct sequences mediate MoKA's cytoplasmic accumulation: one CRM1-dependent leucine-rich export signal and two novel CRM1-independent export signals.
  • The major transcriptional activation domain of MoKA was mapped to a highly acidic region situated between the NLS and NES clusters.

Conclusions:

  • MoKA's intracellular trafficking is regulated by a specific NLS and multiple NESs, including novel CRM1-independent pathways.
  • The identified acidic domain is crucial for MoKA's transcriptional co-activation function.
  • These findings provide critical insights into the molecular mechanisms governing MoKA's role in neuronal differentiation.

More Related Videos

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development09:32

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development

Published on: June 15, 2017

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers10:28

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Published on: September 20, 2018

Related Concept Videos

Master Transcription Regulators02:23

Master Transcription Regulators

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...
Master Transcription Regulators02:23

Master Transcription Regulators

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...
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

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...
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

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...
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

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 addition of a...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...