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Related Concept Videos

Nuclear Export01:42

Nuclear Export

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The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
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Targeted Cancer Therapies02:57

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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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Nuclear Export of mRNA02:31

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Nuclear Export of mRNA02:31

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Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
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Regulation of Nuclear Protein Sorting01:45

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Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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Nuclear Protein Sorting01:34

Nuclear Protein Sorting

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Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
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Related Experiment Video

Updated: Dec 5, 2025

Subcellular Fractionation of Primary Chronic Lymphocytic Leukemia Cells to Monitor Nuclear/Cytoplasmic Protein Trafficking
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Targeting Nuclear Export Proteins in Multiple Myeloma Therapy.

Nicholas Theodoropoulos1, Guido Lancman2, Ajai Chari3

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

Targeted Oncology
|October 19, 2020
PubMed
Summary

Nuclear export inhibitors, like selinexor, show promise for treating refractory multiple myeloma (MM). These small molecule inhibitors of nuclear export (SINEs) are effective against cancer cells and may improve treatment outcomes.

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Area of Science:

  • Oncology
  • Hematology
  • Molecular Biology

Background:

  • Multiple myeloma (MM) is an incurable plasma cell cancer with frequent relapses and treatment resistance.
  • Refractory MM has a poor prognosis, with median overall survival (OS) of 4-6 months despite recent treatment advances.

Purpose of the Study:

  • To review the emerging role of nuclear export inhibition, specifically CRM1/XPO1 inhibition, as a novel treatment modality for refractory MM.
  • To discuss the development and clinical investigation of small molecule inhibitors of nuclear export (SINEs) in MM.

Main Methods:

  • Review of preclinical studies on SINEs in MM, evaluating their cytotoxicity, role in therapy resensitization, and potential impact on bone disease.
  • Analysis of clinical trial data, including the STORM trial which led to the approval of selinexor for relapsed/refractory MM.
  • Examination of ongoing trials investigating selinexor in combination regimens and early trials of second-generation SINEs like eltanexor.

Main Results:

  • Preclinical studies demonstrate SINEs are cytotoxic to myeloma cells, can resensitize tumors to therapy, and may limit bone disease progression.
  • Selinexor, the first nuclear export inhibitor, was approved in July 2019 for relapsed/refractory MM.
  • Eltanexor, a second-generation SINE, shows preliminary efficacy with a potentially improved toxicity profile.

Conclusions:

  • Nuclear export inhibition represents a promising novel therapeutic strategy for refractory multiple myeloma.
  • Ongoing clinical trials are crucial for defining the role of SINEs, including selinexor and eltanexor, in MM treatment paradigms.