Tumor-derived neomorphic mutations in ASXL1 impairs the BAP1-ASXL1-FOXK1/K2 transcription network.

Protein & Cell
Yu-Kun XiaDan Ye

Abstract

Additional sex combs-like 1 (ASXL1) interacts with BRCA1-associated protein 1 (BAP1) deubiquitinase to oppose the polycomb repressive complex 1 (PRC1)-mediated histone H2A ubiquitylation. Germline BAP1 mutations are found in a spectrum of human malignancies, while ASXL1 mutations recurrently occur in myeloid neoplasm and are associated with poor prognosis. Nearly all ASXL1 mutations are heterozygous frameshift or nonsense mutations in the middle or to a less extent the C-terminal region, resulting in the production of C-terminally truncated mutant ASXL1 proteins. How ASXL1 regulates specific target genes and how the C-terminal truncation of ASXL1 promotes leukemogenesis are unclear. Here, we report that ASXL1 interacts with forkhead transcription factors FOXK1 and FOXK2 to regulate a subset of FOXK1/K2 target genes. We show that the C-terminally truncated mutant ASXL1 proteins are expressed at much higher levels than the wild-type protein in ASXL1 heterozygous leukemia cells, and lose the ability to interact with FOXK1/K2. Specific deletion of the mutant allele eliminates the expression of C-terminally truncated ASXL1 and increases the association of wild-type ASXL1 with BAP1, thereby restoring the expression of BAP1-ASXL1-FOXK...Continue Reading

References

Mar 18, 2009·Bioinformatics·Cole TrapnellSteven L Salzberg
Oct 10, 2009·The Journal of Biological Chemistry·Yuichi J MachidaAnindya Dutta
May 4, 2010·Nature·Johanna C ScheuermannJürg Müller
Jul 21, 2011·Carcinogenesis·Koji NishizawaOsamu Ogawa
Mar 23, 2012·Journal of Hematology & Oncology·Véronique Gelsi-BoyerDaniel Birnbaum
May 31, 2012·Bioinformatics·Luis Sanchez-PulidoChris P Ponting
Aug 11, 2012·Science·Anwesha DeyVishva M Dixit
Sep 22, 2012·Science·Anne E White, J Wade Harper
Aug 24, 2013·Hereditary Cancer in Clinical Practice·Katarzyna Labno-KirszniokJan Lubinski
Nov 13, 2013·The Journal of Clinical Investigation·Daichi InoueToshio Kitamura
Nov 13, 2013·The Journal of Experimental Medicine·Omar Abdel-WahabRoss L Levine
Dec 24, 2014·Nature Reviews. Cancer·Lucy GossageEamonn R Maher
Jun 23, 2015·Nature Communications·Anand BalasubramaniAnjana Rao
Jan 7, 2016·Japanese Journal of Clinical Oncology·Taotao SunCaijie Shen
Jan 8, 2016·Nature Communications·Danny D SahtoeTitia K Sixma
Aug 17, 2016·Cold Spring Harbor Perspectives in Medicine·Jean-Baptiste Micol, Omar Abdel-Wahab
Jan 24, 2017·Leukemia·E M HeathA D Schimmer
Feb 22, 2017·Leukemia·C Dell'AversanaL Altucci
Jan 10, 2018·Frontiers in Microbiology·Skyla A DuncanVida A Dennis
Apr 13, 2018·The Journal of Experimental Medicine·Reina NagaseToshio Kitamura
Jul 18, 2018·Nature Communications·Shuhei AsadaToshio Kitamura
Jan 22, 2019·Nature Communications·Antoine CampagneRaphaël Margueron
Feb 1, 2019·Nature·Valentina SukoninaSven Enerbäck
Feb 13, 2019·Journal of Experimental & Clinical Cancer Research : CR·Xiaozhi LiYunhui Liu

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Citations

Oct 28, 2020·International Journal of Molecular Sciences·Cameron J ReddingtonPeter D Mace
Apr 3, 2021·Frontiers in Molecular Biosciences·Lei CaoXudong Wu

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