FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1733138811> ?p ?o ?g. }

• W1733138811 abstract "Still a major challenge in the hematopoietic stem cell biology is to precisely determine the factors that regulate self-renewal and lineage commitment of hematopoietic stem and progenitor cells (HSPCs). A better understanding of the mechanisms regulating HSPCs is required, because of their clinical therapeutic applications and their aberrant regulation during leukemia. AC133 is a (117 kD) pentaspan transmembrane surface glycoprotein, a specific glycoform of CD133 (prominin-1) predominantly expressed on a subset of CD34+ and a small fraction of CD34– HSPCs. AC133+ HSPCs are enriched for colony-forming units (CFUs), long-term culture initiating cells (LTC-IC) and are capable of hematopoietic reconstitution. Beyond that, AC133 is used for prospective isolation of tumour-initiating cells in certain hematologic malignancies. However, the mechanism underlying the expression of AC133 and CD133 needs to be further explored. CD133 is transcribed from alternative tissue dependent promoters, and of these promoters, P1 is active in HSPCs as opposed to differentiated hematopoietic cells, and this is paralleled by CD133 mRNA and protein levels. Recently, a direct link of CD133 expression with activation of Wnt / -catenin and PI3K / Akt signaling was shown (Mak et al., 2012; Wei et al., 2013). Wnt signaling strength regulates normal haematopoiesis, and its deregulation is involved in leukemia development. Therefore, working out mechanisms controlling AC133 expression and other mechanisms influencing the functional properties of HSPCs is important to understand homeostasis in normal and dysregulated hematopoietic tissue at molecular level. In a previous study from our research group, it came out that nucleolin act as a CD34 promoter factor, and was found to be enriched in mobilized peripheral blood (MPB)-derived undifferentiated CD34+ HSPCs as opposed to differentiated CD34– cells (Grinstein et al., 2007). Nucleolin is a multifunctional nucleolar phosphoprotein, overexpressed in actively growing and cancer cells, involved in transcriptional regulation, chromatin remodeling, and RNA metabolism. Aberrant activity of nucleolin is generally associated with several haematological malignancies. The present study dissects nucleolin-dependent activation of AC133 and CD133 expression via promoter P1 in MPB-derived CD34+ HSPCs and in leukemic cell line models. Overexpression of nucleolin was likely associated with polarization in HSPCs, and was probably resulted from higher cellular PI3K / Akt levels. In CD34+ HSPCs and in an acute myeloid leukemia (AML) derived cell line Mutz-2; nucleolin elevates hematopoietic CFU frequencies and predominately impacts common primitive granulocytes-macrophage (GM) progenitors. In down-modulation experiments, silencing of nucleolin in Mutz-2 cells leads to the early differentiation, and into a myeloid phenotype. Furthermore, in HSPCs; nucleolin amplifies numbers of LTC-IC and supported long-term maintenance of hematopoietic progenitors in cytokine-dependent stroma-free cultures. Beyond that, growth promoting effects of nucleolin extended to lymphoid lineage as well, with an increase output of CD19+ & CD34+CD19+ cells under conditions permissive for B lymphoid development. Levels of active β-catenin (Wnt / β-catenin), active Akt (PI3K / Akt) and BCL-2 in HSPCs are nucleolin dependent and functional effects of nucleolin on HSPCs partially relies on β-catenin activity. Wnt/β-catenin and BCL-2 is found to be aberrantly activated in leukemia, providing opportunities for therapeutic intervention. In addition, elevated levels of nucleolin stabilize bcl-2 mRNA in leukemic cells, which allows cells to overproduce BCL-2 and thereby protecting them from apoptosis. Overall, this report strongly indicates that the deregulation of nucleolin via activation of Wnt / β-catenin, and BCL-2 can be implicated in leukemia, and providing opportunities for therapeutic interventions." @default.
• W1733138811 created "2016-06-24" @default.
• W1733138811 creator A5039439291 @default.
• W1733138811 date "2015-01-01" @default.
• W1733138811 modified "2023-09-26" @default.
• W1733138811 title "A role of nucleolin in human hematopoietic progenitor cells" @default.
• W1733138811 hasPublicationYear "2015" @default.
• W1733138811 type Work @default.
• W1733138811 sameAs 1733138811 @default.
• W1733138811 citedByCount "0" @default.
• W1733138811 crossrefType "journal-article" @default.
• W1733138811 hasAuthorship W1733138811A5039439291 @default.
• W1733138811 hasConcept C10205521 @default.
• W1733138811 hasConcept C109159458 @default.
• W1733138811 hasConcept C137620995 @default.
• W1733138811 hasConcept C201750760 @default.
• W1733138811 hasConcept C203014093 @default.
• W1733138811 hasConcept C28328180 @default.
• W1733138811 hasConcept C502942594 @default.
• W1733138811 hasConcept C62478195 @default.
• W1733138811 hasConcept C86803240 @default.
• W1733138811 hasConcept C95444343 @default.
• W1733138811 hasConcept C99854124 @default.
• W1733138811 hasConceptScore W1733138811C10205521 @default.
• W1733138811 hasConceptScore W1733138811C109159458 @default.
• W1733138811 hasConceptScore W1733138811C137620995 @default.
• W1733138811 hasConceptScore W1733138811C201750760 @default.
• W1733138811 hasConceptScore W1733138811C203014093 @default.
• W1733138811 hasConceptScore W1733138811C28328180 @default.
• W1733138811 hasConceptScore W1733138811C502942594 @default.
• W1733138811 hasConceptScore W1733138811C62478195 @default.
• W1733138811 hasConceptScore W1733138811C86803240 @default.
• W1733138811 hasConceptScore W1733138811C95444343 @default.
• W1733138811 hasConceptScore W1733138811C99854124 @default.
• W1733138811 hasLocation W17331388111 @default.
• W1733138811 hasOpenAccess W1733138811 @default.
• W1733138811 hasPrimaryLocation W17331388111 @default.
• W1733138811 hasRelatedWork W102737129 @default.
• W1733138811 hasRelatedWork W1548081699 @default.
• W1733138811 hasRelatedWork W1660819588 @default.
• W1733138811 hasRelatedWork W1894029484 @default.
• W1733138811 hasRelatedWork W1978112398 @default.
• W1733138811 hasRelatedWork W2059091911 @default.
• W1733138811 hasRelatedWork W2109048121 @default.
• W1733138811 hasRelatedWork W2114929247 @default.
• W1733138811 hasRelatedWork W2187875300 @default.
• W1733138811 hasRelatedWork W2268585250 @default.
• W1733138811 hasRelatedWork W2465024687 @default.
• W1733138811 hasRelatedWork W2500382903 @default.
• W1733138811 hasRelatedWork W2582139488 @default.
• W1733138811 hasRelatedWork W2692814333 @default.
• W1733138811 hasRelatedWork W2728473578 @default.
• W1733138811 hasRelatedWork W2886737665 @default.
• W1733138811 hasRelatedWork W2917188245 @default.
• W1733138811 hasRelatedWork W2979784225 @default.
• W1733138811 hasRelatedWork W3095933316 @default.
• W1733138811 hasRelatedWork W2402786643 @default.
• W1733138811 isParatext "false" @default.
• W1733138811 isRetracted "false" @default.
• W1733138811 magId "1733138811" @default.
• W1733138811 workType "article" @default.