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Insertional Mutagenesis Identifies a STAT3/Arid1b/ b-catenin Pathway Driving Neurofibroma Initiation

Type:: Article
Description/Abstract:: Wu et al. map an Nf1-Stat3-Arid1b/ b-catenin pathway that initiates Neurofibromatosis type 1 (Nf1) neurofibromas, using unbiased insertional mutagenesis screening. Stat3 transcriptionally represses Gsk3b and Arid1b, thereby activating b-catenin in Schwann cell precursors and resulting in neurofibroma initiation and maintenance. Stat3-mediated modification plays a role in early tumorigenesis.
Creator/Author:: Spinner, R. J.; Ratner, N.; Largaespada, D. A.; Keng, V.; Patmore, D. M.; Wu, J., and Cancelas, Jose A.
Submitter:: Jose Cancelas
Date Uploaded:: 02/08/2017
Date Modified:: 04/10/2017
Date Created:: 2016-02
License:: All rights reserved

Myeloid Malignancies with Chromosome 5q Deletions Acquire a Dependency on an Intrachromosomal NF-kB Gene Network

Type:: Article
Description/Abstract:: Chromosome 5q deletions (del[5q]) are common in high-risk (HR) myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML); however, the gene regulatory networks that sustain these aggressive diseases are unknown. Reduced miR-146a expression in del(5q) HR MDS/AML and miR-146a/ hematopoietic stem/progenitor cells (HSPCs) results in TRAF6/NF-kB activation. Increased survival and proliferation of HSPCs from miR-146alow HR MDS/AML is sustained by a neighboring haploid gene, SQSTM1 (p62), expressed from the intact 5q allele. Overexpression of p62 from the intact allele occurs through NF-kB-dependent feedforward signaling mediated by miR-146a deficiency. p62 is necessary for TRAF6-mediated NF-kB signaling, as disrupting the p62-TRAF6 signaling complex results in cell-cycle arrest and apoptosis of MDS/AML cells. Thus, del(5q) HR MDS/AML employs an intrachromosomal gene network involving loss of miR-146a and haploid overexpression of p62 via NF-kB to sustain TRAF6/NF-kB signaling for cell survival and proliferation. Interfering with the p62-TRAF6 signaling complex represents a therapeutic option in miR-146a-deficient and aggressive del(5q) MDS/AML.
Creator/Author:: Komurov, K.; Maciejewski, J. P.; Bolanos, L.; Grimes, H. L.; Cancelas, Jose A.; Chen, X.; Barker, B.; Weirauch, M. T.; Jerez, A.; Liu, X.; Makishima, H.; Christie, S.; Starczynowski, D. T.; Rao, D. S., and Fang, J.
Submitter:: Jose Cancelas
Date Uploaded:: 02/08/2017
Date Modified:: 04/10/2017
Date Created:: 2014-09
License:: All rights reserved

P62 is Required for Stem Cell/Progenitor Retention through Inhahvition of IKK/NF-kB/CcI14 Signaling at the Bone Marrow Macrophage-Osteoblast Niche

Article thumbnail: P62 is Required for Stem Cell/Progenitor Retention through Inhahvition of IKK/NF-kB/CcI14 Signaling at the Bone Marrow Macrophage-Osteoblast Niche

Type:: Article
Description/Abstract:: Not Available
Creator/Author:: Moscat, J.; Nayak, R. C.; Aronow, B.; Duran, A., and Cancelas, Jose A.
Submitter:: Jose Cancelas
Date Uploaded:: 02/08/2017
Date Modified:: 04/10/2017
Date Created:: 2014-12

Insertional Mutagenesis Identifies a STAT3/Arid1b/ b-catenin Pathway Driving Neurofibroma Initiation

Myeloid Malignancies with Chromosome 5q Deletions Acquire a Dependency on an Intrachromosomal NF-kB Gene Network

P62 is Required for Stem Cell/Progenitor Retention through Inhahvition of IKK/NF-kB/CcI14 Signaling at the Bone Marrow Macrophage-Osteoblast Niche

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