Next Article in Journal
Roles of Autophagy-Related Genes in the Pathogenesis of Inflammatory Bowel Disease
Next Article in Special Issue
Hutchinson-Gilford Progeria Syndrome—Current Status and Prospects for Gene Therapy Treatment
Previous Article in Journal
Development of a Bicistronic Vector for the Expression of a CRISPR/Cas9-mCherry System in Fish Cell Lines
Previous Article in Special Issue
Controlling the Gatekeeper: Therapeutic Targeting of Nuclear Transport
Article Menu
Issue 1 (January) cover image

Export Article

Open AccessFeature PaperReview
Cells 2019, 8(1), 76;

NUP214 in Leukemia: It’s More than Transport

Institute of Biology and Molecular Medicine, Université Libre de Bruxelles, 6041 Charleroi, Belgium
Author to whom correspondence should be addressed.
Received: 27 November 2018 / Revised: 10 January 2019 / Accepted: 17 January 2019 / Published: 21 January 2019
(This article belongs to the Special Issue Nuclear Transport in Ageing and Diseases)
Full-Text   |   PDF [1910 KB, uploaded 21 January 2019]   |  
  |   Review Reports


NUP214 is a component of the nuclear pore complex (NPC) with a key role in protein and mRNA nuclear export. Chromosomal translocations involving the NUP214 locus are recurrent in acute leukemia and frequently fuse the C-terminal region of NUP214 with SET and DEK, two chromatin remodeling proteins with roles in transcription regulation. SET-NUP214 and DEK-NUP214 fusion proteins disrupt protein nuclear export by inhibition of the nuclear export receptor CRM1, which results in the aberrant accumulation of CRM1 protein cargoes in the nucleus. SET-NUP214 is primarily associated with acute lymphoblastic leukemia (ALL), whereas DEK-NUP214 exclusively results in acute myeloid leukemia (AML), indicating different leukemogenic driver mechanisms. Secondary mutations in leukemic blasts may contribute to the different leukemia outcomes. Additional layers of complexity arise from the respective functions of SET and DEK in transcription regulation and chromatin remodeling, which may drive malignant hematopoietic transformation more towards ALL or AML. Another, less frequent fusion protein involving the C terminus of NUP214 results in the sequestosome-1 (SQSTM1)-NUP214 chimera, which was detected in ALL. SQSTM1 is a ubiquitin-binding protein required for proper autophagy induction, linking the NUP214 fusion protein to yet another cellular mechanism. The scope of this review is to summarize the general features of NUP214-related leukemia and discuss how distinct chromosomal translocation partners can influence the cellular effects of NUP214 fusion proteins in leukemia. View Full-Text
Keywords: NUP214; SET; DEK; leukemia; HOX genes; CRM1; nucleocytoplasmic transport; chromatin remodeling; transcription NUP214; SET; DEK; leukemia; HOX genes; CRM1; nucleocytoplasmic transport; chromatin remodeling; transcription

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Mendes, A.; Fahrenkrog, B. NUP214 in Leukemia: It’s More than Transport. Cells 2019, 8, 76.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Cells EISSN 2073-4409 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top