A balance between Raf-1 and Fas expression sets the pace of erythroid differentiation

Blood
Cristina RubioloM Baccarini

Abstract

Normal erythropoiesis critically depends on the balance between the renewal of precursor cells and their differentiation. If the renewal phase is shortened, the decrease in the precursor pool results in anemia; conversely, impaired differentiation increases the number of proliferating progenitors and the potential risk of leukemic transformation. Using gene ablation, we have discovered 2 self-sustaining signal transduction loops that antagonize each other and regulate erythroid progenitor proliferation and differentiation, respectively. We identify Raf-1 as the main activator of the MEK/ERK cascade and as the key molecule in maintaining progenitor proliferation. Differentiation, in contrast, is mediated by Fas via the activation of both the ASK1/JNK/p38 module and the caspase cascade. The point of convergence between the 2 cascades is activated ERK, which positively feeds back on the proliferation pathway by maintaining the expression of Raf-1, while inhibiting the expression of Fas and therefore differentiation. In turn, Fas, once expressed, antagonizes proliferation by exerting a negative feedback on ERK activation and Raf-1 expression. Simultaneously, Fas-mediated caspase activation precipitates differentiation. These result...Continue Reading

References

May 1, 1994·Leukemia & Lymphoma·R LiangD Todd
Feb 14, 1998·The Journal of Cell Biology·Y IshizakiM C Raff
Dec 2, 1999·Genes & Development·A BauerH Beug
Feb 24, 2001·Archives of Histology and Cytology·K ChoK Kaneda
Feb 24, 2001·The Journal of Experimental Medicine·Y ZermatiO Hermine
Jun 28, 2001·Proceedings of the National Academy of Sciences of the United States of America·J ChenH Fu
Sep 3, 2002·Cancer Cell·Heather L MaeckerAmato J Giaccia
Oct 23, 2002·Leukemia & Lymphoma·Wojciech KalasLeon Strzadala
Nov 20, 2002·The Journal of Experimental Medicine·Andrea KolbusManuela Baccarini
Dec 17, 2002·Experimental Hematology·Faris Q B AlenziMyrtle Y Gordon
Apr 8, 2004·Molecular Cell·Maria Julia MarinissenJ Silvio Gutkind
Mar 9, 2005·The Journal of Cell Biology·Karin EhrenreiterManuela Baccarini
Mar 16, 2005·Cell·Steven M JohnsonFrank J Slack
Mar 31, 2005·Current Opinion in Genetics & Development·Amy E PasquinelliJohn Bracht
Apr 19, 2005·Nature Neuroscience·Jean-Michel RevestPier Vincenzo Piazza
Dec 21, 2005·The Journal of Cell Biology·Daniela PiazzollaManuela Baccarini

❮ Previous
Next ❯

Citations

Apr 23, 2013·Bioprocess and Biosystems Engineering·Tran Hong Ha PhanMayasari Lim
Aug 2, 2013·Acta Biotheoretica·P KurbatovaV Volpert
Jan 1, 2010·Journal of Biological Dynamics·I DeminV Volpert
Sep 22, 2007·Annual Review of Pharmacology and Toxicology·Kohsuke TakedaHidenori Ichijo
Jul 23, 2011·Genes & Cancer·David MatallanasWalter Kolch
Oct 29, 2010·Human Genomics and Proteomics : HGP·Ofer EidelmanHarvey B Pollard
Apr 29, 2010·Hematology·Monika HorvathovaVladimir Divoky
Dec 10, 2015·Experimental Hematology·Mark J Koury
Jul 14, 2010·Trends in Biochemical Sciences·Reiner Wimmer, Manuela Baccarini
Jan 2, 2010·Journal of Theoretical Biology·Fabien CrausteVitaly Volpert
Jul 28, 2007·Critical Reviews in Oncology/hematology·Vivien M HodgesA Peter Maxwell
Dec 24, 2009·Molecular Systems Biology·Marcel SchillingUrsula Klingmüller
Sep 18, 2015·Immunologic Research·Jimmy HomLionel Blanc
Mar 12, 2015·Bioscience Reports·Elena B KostovaRobin van Bruggen
Jun 10, 2015·Nature Reviews. Nephrology·Mark J Koury, Volker H Haase
Apr 19, 2015·Blood·David Kuhrt, Don M Wojchowski
Feb 6, 2014·Journal of Mathematical Biology·N EymardV Volpert
Nov 20, 2016·The FEBS Journal·Daniela SiegmundHarald Wajant
Nov 6, 2018·Molecular Human Reproduction·Katharina ProestlingLorenz Kuessel
Nov 10, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Pasan Fernando, Lynn A Megeney
Jan 17, 2020·Cells·Ufuk DegirmenciJiancheng Hu
Aug 19, 2020·Journal of Hematology & Oncology·Jimin YuanJiancheng Hu
Aug 3, 2019·Der Anaesthesist·C RosenthalL Kaufner
Aug 28, 2021·International Journal of Molecular Sciences·Iveta YotovaRené Wenzl

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.