Biomaterial Database

The p53 tumor suppressor protein regulates hematopoietic stem cell fate. 2011

Takashi Asai, and Yan Liu, and Narae Bae, and Stephen D Nimer

Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.

The p53 tumor suppressor protein is a key transcription factor that regulates several signaling pathways involved in the cell's response to stress. Through stress-induced activation, p53 accumulates and triggers the expression of target genes that protect the genetic integrity of all cells including hematopoietic stem cells (HSCs). These protective mechanisms include cell-cycle arrest, DNA repair, induction of apoptosis, or initiation of senescence. In addition to its function under stress conditions, p53 has important functions during steady-state hematopoiesis, regulating HSC quiescence and self-renewal. In addition, it appears that p53 levels affect HSC competition for the hematopoietic niche, with the less p53 activated HSCs preferentially surviving. The specific genes and precise mechanisms underlying p53's effects on normal HSCs are slowly being clarified. p53 also plays an important role in leukemia stem cell (LSC) behavior, with p53 loss affecting drug resistance and disease progression. Pharmacologic activation of p53 function could overcome the adverse impact of p53 inactivation in LSCs. Thus, understanding the p53 regulatory mechanisms active in HSCs and LSCs may promote the development of new therapeutic strategies that could eliminate the population of largely quiescent LSCs.

UI	MeSH Term	Description	Entries
D006412	Hematopoietic Stem Cells	Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood.	Colony-Forming Units, Hematopoietic,Progenitor Cells, Hematopoietic,Stem Cells, Hematopoietic,Hematopoietic Progenitor Cells,Cell, Hematopoietic Progenitor,Cell, Hematopoietic Stem,Cells, Hematopoietic Progenitor,Cells, Hematopoietic Stem,Colony Forming Units, Hematopoietic,Colony-Forming Unit, Hematopoietic,Hematopoietic Colony-Forming Unit,Hematopoietic Colony-Forming Units,Hematopoietic Progenitor Cell,Hematopoietic Stem Cell,Progenitor Cell, Hematopoietic,Stem Cell, Hematopoietic,Unit, Hematopoietic Colony-Forming,Units, Hematopoietic Colony-Forming
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013312	Stress, Physiological	The unfavorable effect of environmental factors (stressors) on the physiological functions of an organism. Prolonged unresolved physiological stress can affect HOMEOSTASIS of the organism, and may lead to damaging or pathological conditions.	Biotic Stress,Metabolic Stress,Physiological Stress,Abiotic Stress,Abiotic Stress Reaction,Abiotic Stress Response,Biological Stress,Metabolic Stress Response,Physiological Stress Reaction,Physiological Stress Reactivity,Physiological Stress Response,Abiotic Stress Reactions,Abiotic Stress Responses,Abiotic Stresses,Biological Stresses,Biotic Stresses,Metabolic Stress Responses,Metabolic Stresses,Physiological Stress Reactions,Physiological Stress Responses,Physiological Stresses,Reaction, Abiotic Stress,Reactions, Abiotic Stress,Response, Abiotic Stress,Response, Metabolic Stress,Stress Reaction, Physiological,Stress Response, Metabolic,Stress Response, Physiological,Stress, Abiotic,Stress, Biological,Stress, Biotic,Stress, Metabolic
D014411	Neoplastic Stem Cells	Highly proliferative, self-renewing, and colony-forming stem cells which give rise to NEOPLASMS.	Cancer Stem Cells,Colony-Forming Units, Neoplastic,Stem Cells, Neoplastic,Tumor Stem Cells,Neoplastic Colony-Forming Units,Tumor Initiating Cells,Cancer Stem Cell,Cell, Cancer Stem,Cell, Neoplastic Stem,Cell, Tumor Initiating,Cell, Tumor Stem,Cells, Cancer Stem,Cells, Neoplastic Stem,Cells, Tumor Initiating,Cells, Tumor Stem,Colony Forming Units, Neoplastic,Colony-Forming Unit, Neoplastic,Initiating Cell, Tumor,Initiating Cells, Tumor,Neoplastic Colony Forming Units,Neoplastic Colony-Forming Unit,Neoplastic Stem Cell,Stem Cell, Cancer,Stem Cell, Neoplastic,Stem Cell, Tumor,Stem Cells, Cancer,Stem Cells, Tumor,Tumor Initiating Cell,Tumor Stem Cell,Unit, Neoplastic Colony-Forming,Units, Neoplastic Colony-Forming
D016159	Tumor Suppressor Protein p53	Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.	p53 Tumor Suppressor Protein,Cellular Tumor Antigen p53,Oncoprotein p53,TP53 Protein,TRP53 Protein,p53 Antigen,pp53 Phosphoprotein,Phosphoprotein, pp53
D016922	Cellular Senescence	Process by which cells irreversibly stop dividing and enter a state of permanent growth arrest without undergoing CELL DEATH. Senescence can be induced by DNA DAMAGE or other cellular stresses, such as OXIDATIVE STRESS.	Aging, Cell,Cell Aging,Cell Senescence,Replicative Senescence,Senescence, Cellular,Senescence, Replicative,Cell Ageing,Cellular Ageing,Cellular Aging,Ageing, Cell,Ageing, Cellular,Aging, Cellular,Senescence, Cell
D019070	Cell Lineage	The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo.	Cell Lineages,Lineage, Cell,Lineages, Cell