WFRF:(Hertwig Falk)
Search: WFRF:(Hertwig Falk) > SMAD4 binds HOXA9 i...
- 11 of 12
- Previous record
- Next record
- To hitlist
SMAD4 binds HOXA9 in the cytoplasm and protects primitive hematopoietic cells against nuclear activation by HOXA9 and leukemia transformation.
-
- Quere, Ronan (author)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine
-
- Karlsson, Göran (author)
- Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine
-
- Hertwig, Falk (author)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine
- show more...
- Vandenberghe, Peter (author)
- Slovak, Marilyn L (author)
- show less...
- (creator_code:org_t)
- American Society of Hematology, 2011
- 2011
- English.
- In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 117, s. 5918-5930
- Journal article (peer-reviewed)
Abstract
Subject headings
Close
- We studied leukemic stem cells (LSCs) in a Smad4(-/-) mouse model of acute myelogenous leukemia (AML) induced either by the HOXA9 gene or by the fusion oncogene NUP98-HOXA9. While HOXA9-SMAD4 complexes accumulate in the cytoplasm of normal hematopoietic stem- and progenitor cells (HSPCs) transduced with these oncogenes, there is no cytoplasmic accumulation of HOXA9 in Smad4(-/-) HSPCs and as a consequence increased levels of HOXA9 accumulate in the nucleus leading to increased immortalization in vitro. Loss of Smad4 accelerates the development of leukemia in vivo due to an increase in transformation of HSPCs. Therefore, the cytoplasmic binding of HOXA9 by SMAD4 is a mechanism to protect HOXA9-induced transformation of normal HSPCs. Since Smad4 is a potent tumor suppressor involved in growth control, we developed a strategy to modify the subcellular distribution of SMAD4. We successfully disrupted the interaction between HOXA9 and SMAD4 to activate the TGF-beta pathway and apoptosis, leading to a loss of LSCs. Together, these findings reveal a major role for Smad4 in the negative regulation of leukemia initiation and maintenance induced by HOXA9/NUP98-HOXA9 and provide strong evidence that antagonizing SMAD4 stabilization by these oncoproteins might be a promising novel therapeutic approach in leukemia.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
- 11 of 12
- Previous record
- Next record
- To hitlist
Find more in SwePub
- By the author/editor
- Quere, Ronan
- Karlsson, Göran
- Hertwig, Falk
- Rissler, Mariann ...
- Lindqvist, Beata
- Fioretos, Thoas
- show more...
- Vandenberghe, Pe ...
- Slovak, Marilyn ...
- Cammenga, Jörg
- Karlsson, Stefan
- show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
- MEDICAL AND HEAL ...
- and Clinical Medicin ...
- and Hematology
- Articles in the publication
- Blood
- By the university
- Lund University
Search outside SwePub
- Extend your search to:
- Google Book Search
- Google Scholar
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
- Copyright © LIBRIS - National Library Systems
- LIBRIS.kb.se
