Exportin 1 (XPO1), also known as chromosome maintenance 1 protein (CRM1), is the main transporter for hundreds of proteins like tumor suppressors, growth regulatory factors, oncoprotein mRNAs and others. Its upregulation leads to the inactivation of the tumor suppressor anti-neoplastic function in many cancers and logically is associated with poor prognosis. Selective inhibitors of nuclear export (SINE) are a new generation of XPO1 inhibitors that are being investigated as a promising targeted anti-cancer therapy. Selinexor is the first generation of SINE compounds that is being evaluated in many clinical trials involving solid tumors and hematological malignancies with its two approved indications for relapsed multiple myeloma and relapsed diffuse large B-cell lymphoma. Here, we comprehensively review the current knowledge of selinexor and next generations of the SINE compounds in lymphoid and myeloid malignancies.

• Klíčová slova
• Exportin 1 protein, Leukemia, Lymphoma, Myeloma, Selective inhibitors of nuclear export, Selinexor,
• MeSH
• aktivní transport - buněčné jádro účinky léků   MeSH
• cílená molekulární terapie MeSH
• hematologické nádory diagnóza   farmakoterapie   etiologie   mortalita   MeSH
• hydraziny farmakologie   terapeutické užití   MeSH
• karyoferiny antagonisté a inhibitory   MeSH
• lidé MeSH
• management nemoci MeSH
• prognóza MeSH
• protein exportin 1 MeSH
• protinádorové látky farmakologie   terapeutické užití   MeSH
• receptory cytoplazmatické a nukleární antagonisté a inhibitory   MeSH
• triazoly farmakologie   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• hydraziny MeSH
• karyoferiny MeSH
• protinádorové látky MeSH
• receptory cytoplazmatické a nukleární MeSH
• selinexor MeSH Prohlížeč
• triazoly MeSH

Microtubules of all eukaryotic cells are formed by α- and β-tubulin heterodimers. In addition to the well known cytoplasmic tubulins, a subpopulation of tubulin can occur in the nucleus. So far, the potential function of nuclear tubulin has remained elusive. In this work, we show that α- and β-tubulins of various organisms contain multiple conserved nuclear export sequences, which are potential targets of the Exportin 1/CRM1 pathway. We demonstrate exemplarily that these NES motifs are sufficient to mediate export of GFP as model cargo and that this export can be inhibited by leptomycin B, an inhibitor of the Exportin 1/CRM1 pathway. Likewise, leptomycin B causes accumulation of GFP-tagged tubulin in interphase nuclei, in both plant and animal model cells. Our analysis of nuclear tubulin content supports the hypothesis that an important function of nuclear tubulin export is the exclusion of tubulin from interphase nuclei, after being trapped by nuclear envelope reassembly during telophase.

• MeSH
• aktivní transport - buněčné jádro fyziologie   MeSH
• buněčné jádro metabolismus   MeSH
• buněčné linie MeSH
• cytoplazma metabolismus   MeSH
• eukaryotické buňky metabolismus   MeSH
• karyoferiny metabolismus   MeSH
• lidé MeSH
• mikrotubuly metabolismus   MeSH
• protein exportin 1 MeSH
• receptory cytoplazmatické a nukleární metabolismus   MeSH
• tabák metabolismus   MeSH
• transport proteinů fyziologie   MeSH
• tubulin metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• karyoferiny MeSH
• receptory cytoplazmatické a nukleární MeSH
• tubulin MeSH