scholarly journals Fanconi Anemia Group D2 Protein

2020 ◽  
Author(s):  
Keyword(s):  
Fanconi Anemia ◽  
Anemia Group ◽  
D2 Protein

scholarly journals Functional Correction of Fanconi Anemia Group C Hematopoietic Cells by the Use of a Novel Lentiviral Vector

2001 ◽  
Vol 3 (4) ◽  
pp. 485-490 ◽  
Author(s):  
Kaoru Yamada ◽  
John C. Olsen ◽  
Manij Patel ◽  
Kathleen W. Rao ◽  
Christopher E. Walsh
Keyword(s):  
Fanconi Anemia ◽  
Lentiviral Vector ◽  
Hematopoietic Cells ◽  
Functional Correction ◽  
Anemia Group

scholarly journals Engraftment of Hematopoietic Progenitor Cells Transduced with the Fanconi Anemia Group C Gene (FANCC)

1999 ◽  
Vol 10 (14) ◽  
pp. 2337-2346 ◽  
Author(s):  
Johnson M. Liu ◽  
Sonnie Kim ◽  
Elizabeth J. Read ◽  
Makoto Futaki ◽  
Inderjeet Dokal ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Fanconi Anemia ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Anemia Group

Fanconi anemia group A and C double-mutant mice

2002 ◽  
Vol 30 (7) ◽  
pp. 679-688 ◽  
Author(s):  
Meenakshi Noll ◽  
Kevin P Battaile ◽  
Raynard Bateman ◽  
Timothy P Lax ◽  
Keany Rathbun ◽  
...  
Keyword(s):  
Fanconi Anemia ◽  
Double Mutant ◽  
Mutant Mice ◽  
Group A ◽  
Anemia Group

scholarly journals Acetylation modulates the Fanconi anemia pathway by protecting FAAP20 from ubiquitin-mediated proteasomal degradation

2020 ◽  
Vol 295 (40) ◽  
pp. 13887-13901
Author(s):  
Bhavika Nagareddy ◽  
Arafat Khan ◽  
Hyungjin Kim
Keyword(s):  
Fanconi Anemia ◽  
Posttranslational Modifications ◽  
Genome Stability ◽  
Chromosome Instability ◽  
Lysine Residue ◽  
Core Complex ◽  
Ubiquitin E3 Ligase ◽  
Pathway Activation ◽  
Anemia Group ◽  
Inherited Mutations

Fanconi anemia (FA) is a chromosome instability syndrome of children caused by inherited mutations in one of FA genes, which together constitute a DNA interstrand cross-link (ICL) repair, or the FA pathway. Monoubiquitination of Fanconi anemia group D2 protein (FANCD2) by the multisubunit ubiquitin E3 ligase, the FA core complex, is an obligate step in activation of the FA pathway, and its activity needs to be tightly regulated. FAAP20 is a key structural component of the FA core complex, and regulated proteolysis of FAAP20 mediated by prolyl cis-trans isomerization and phosphorylation at a consensus phosphodegron motif is essential for preserving the integrity of the FA core complex, and thus FANCD2 monoubiquitination. However, how ubiquitin-dependent FAAP20 degradation is modulated to fine-tune FA pathway activation remains largely un-known. Here, we present evidence that FAAP20 is acetylated by the acetyltransferase p300/CBP on lysine 152, the key residue that when polyubiquitinated results in the degradation of FAAP20. Acetylation or mutation of the lysine residue stabilizes FAAP20 by preventing its ubiquitination, thereby protecting it from proteasome-dependent FAAP20 degradation. Consequently, disruption of the FAAP20 acetylation pathway impairs FANCD2 activation. Together, our study reveals a competition mechanism between ubiquitination and acetylation of a common lysine residue that controls FAAP20 stability and highlights a complex balancing between different posttranslational modifications as a way to refine the FA pathway signaling required for DNA ICL repair and genome stability.

scholarly journals Inactivation of the Fanconi Anemia Group C Gene Augments Interferon-γ–Induced Apoptotic Responses in Hematopoietic Cells

Blood ◽  
1997 ◽  
Vol 90 (3) ◽  
pp. 974-985 ◽  
Author(s):  
R. Keaney Rathbun ◽  
Gregory R. Faulkner ◽  
Marika H. Ostroski ◽  
Tracy A. Christianson ◽  
Grant Hughes ◽  
...  
Keyword(s):  
Fanconi Anemia ◽  
Inhibitory Effect ◽  
Interferon Γ ◽  
Interferon Response ◽  
Low Doses ◽  
Order Of Magnitude ◽  
Ifn Γ ◽  
Fas Pathway ◽  
Anemia Group ◽  
Induced Apoptosis

Abstract Hematopoietic progenitor cells (HPC) from mice nullizygous at the Fanconi anemia (FA) group C locus (FAC −/−) are hypersensitive to the mitotic inhibitory effects of interferon (IFN-γ). We tested the hypothesis that HPC from the bone marrow of Fanconi group C children are similarly hypersensitive and that the fas pathway is involved in affecting programmed cell death in response to low doses of IFN-γ. In normal human and murine HPC, IFN-γ primed the fas pathway and induced both fas and interferon response factor-1 (IRF-1) gene expression. These IFN-γ-induced apoptotic responses in HPC from the marrow of a child with FA of the C group (FA-C) and in FAC −/− mice occurred at significantly lower IFN doses (by an order of magnitude) than did the apoptotic responses of normal HPC. Treatment of FA-C CD34+ cells with low doses of recombinant IFN-γ, inhibited growth of colony forming unit granulocyte-macrophage and burst-forming unit erythroid, while treatment with blocking antibodies to fas augmented clonal growth and abrogated the clonal inhibitory effect of IFN-γ. Transfer of the normal FAC gene into FA-C B-cell lines prevented mitomycin C–induced apoptosis, but did not suppress fas expression or inhibit the primed fas pathway. However, the kinetics of Stat1-phosphate decay in IFN-γ–treated cells was prolonged in mutant cells and was normalized by transduction of the normal FAC gene. Therefore, the normal FAC protein serves, in part, to modulate IFN-γ signals. HPC bearing inactivating mutations of FAC fail to normally modulate IFN-γ signals and, as a result, undergo apoptosis executed through the fas pathway.

Protein Replacement by Receptor-Mediated Endocytosis Corrects the Sensitivity of Fanconi Anemia Group C Cells to Mitomycin C

Blood ◽  
1999 ◽  
Vol 93 (1) ◽  
pp. 363-369 ◽  
Author(s):  
Hagop Youssoufian ◽  
Frank A.E. Kruyt ◽  
Xiaotong Li
Keyword(s):  
Mitomycin C ◽  
Fanconi Anemia ◽  
Hematopoietic Cells ◽  
Chimeric Protein ◽  
Direct Gene Transfer ◽  
C Cells ◽  
Receptor Mediated Endocytosis ◽  
Culture Model ◽  
Complementation Groups ◽  
Anemia Group

Abstract Current methods for direct gene transfer into hematopoietic cells are inefficient. Here we show that functional complementation of Fanconi anemia (FA) group C cells by protein replacement can be as efficacious as by transfection with wild-type FAC cDNA. We expressed a chimeric protein (called His-ILFAC) consisting of the mature coding portion of gibbon interleukin-3 (IL-3) and full-length FAC inEscherichia coli. The purified bacterial protein is internalized by hematopoietic cells via IL-3 receptors. The intracellular half-life of His-ILFAC is approximately 60 minutes, which is comparable to that of the transgene-encoded FAC protein. In this cell-culture model His-ILFAC completely corrects the sensitivity of FA group C cells to mitomycin C, but it has no effect on FA cells that belong to complementation groups A and B. We suggest that receptor-mediated endocytosis of cytokine-fusion proteins may be of general use to deliver macromolecules into hematopoietic progenitor cells.

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