Publication:


abstract

hematopoietic stem cells (HSCs) residing in the bone marrow generate mature blood cells throughout the life of the organism. This is accomplished by careful Regulation of HSC activity to balance quiescence, self-renewal and differentiation. Studies of the molecular mechanisms governing HSC maintenance have mostly focused on the role of signaling and transcriptional processes. However, it has recently been demonstrated that protein regulation via the ubiquitin proteasome system (UPS) is crucial for normal HSC function; the loss of which can lead to transformation and leukemogenesis. The effective use of a general and reversible inhibitor of the UPS, bortezomib, in treating mantle cell lymphoma and multiple myeloma has demonstrated that targeting the UPS has therapeutic potential. Thus, understanding the emerging field of how the UPS regulates HSC activity may lead to novel targets for therapy of leukemia.

Copyright © 2012. Published by Elsevier Ltd.

Related Articles
Review Regulation of hematopoietic stem cell growth.
Leukemia. 2004
Review Regulation of hematopoietic stem cell growth.
Attar EC, Scadden DT. Leukemia. 2004 Nov; 18(11):1760-8.
Review The elements of stem cell self-renewal: a genetic perspective.
Biotechniques. 2003
Review The elements of stem cell self-renewal: a genetic perspective.
Pazianos G, Uqoezwa M, Reya T. Biotechniques. 2003 Dec; 35(6):1240-7.
Review Mechanisms controlling hematopoietic stem cell functions during normal hematopoiesis and hematological malignancies.
Wiley Interdiscip Rev Syst Bio...
Review Mechanisms controlling hematopoietic stem cell functions during normal hematopoiesis and hematological malignancies.
Warr MR, Pietras EM, Passegué E. Wiley Interdiscip Rev Syst Biol Med. 2011 Nov-Dec; 3(6):681-701. Epub 2011 Mar 15.
Rb is dispensable for self-renewal and multilineage differentiation of adult hematopoietic stem cells.
Proc Natl Acad Sci U S A. 2006
Rb is dispensable for self-renewal and multilineage differentiation of adult hematopoietic stem cells.
Walkley CR, Orkin SH. Proc Natl Acad Sci U S A. 2006 Jun 13; 103(24):9057-62. Epub 2006 Jun 5.
The transcriptional coactivator Cbp regulates self-renewal and differentiation in adult hematopoietic stem cells.
Mol Cell Biol. 2011
The transcriptional coactivator Cbp regulates self-renewal and differentiation in adult hematopoietic stem cells.
Chan WI, Hannah RL, Dawson MA, Pridans C, Foster D, Joshi A, Göttgens B, Van Deursen JM, Huntly BJ. Mol Cell Biol. 2011 Dec; 31(24):5046-60. Epub 2011 Oct 17.