Back to Search
Start Over
TIP110/p110nrb/SART3/p110 regulation of hematopoiesis through CMYC.
- Source :
-
Blood [Blood] 2011 May 26; Vol. 117 (21), pp. 5643-51. Date of Electronic Publication: 2011 Mar 29. - Publication Year :
- 2011
-
Abstract
- Intracellular factors are involved in and essential for hematopoiesis. HIV-1 Tat-interacting protein of 110 kDa (TIP110; p110(nrb)/SART3/p110) is an RNA-binding nuclear protein implicated in the regulation of HIV-1 gene and host gene transcription, pre-mRNA splicing, and cancer immunology. In the present study, we demonstrate a role for TIP110 in the regulation of hematopoiesis. TIP110 was expressed in human CD34(+) cells and decreased with differentiation of CD34(+) cells. TIP110 mRNA was also expressed in phenotyped mouse marrow hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). Using TIP110 transgenic (TIP110(TG)) and haploinsufficient (TIP110(+/-)) mice, we found that increased TIP110 expression enhanced HPC numbers, survival, and cell cycling, whereas decreased TIP110 expression had the opposite effects. Moreover, TIP110(+/-) bone marrow HPCs responded more effectively, and TIP110(TG) HPCs less effectively, than those of wild-type control mice to recovery from the cell-cycle-active drug 5-fluorouracil (5-FU). Unexplained sex differences were noted in HSC competitive repopulating ability, but not HPC numbers, in TIP110(TG) mice. Intracellularly, TIP110 regulated CMYC and GATA2 expression at the transcriptional level, and TIP110 and CMYC reciprocally regulated the expression of each other. These results demonstrate a role for TIP110 in the regulation of hematopoiesis, effects that are likely linked to TIP110 regulation of CMYC.
- Subjects :
- Animals
Antimetabolites, Antineoplastic pharmacology
Blotting, Western
Bone Marrow drug effects
Cell Cycle drug effects
Cell Proliferation drug effects
Cell Survival drug effects
Cells, Cultured
Female
Fetal Blood metabolism
Fluorouracil pharmacology
GATA2 Transcription Factor genetics
GATA2 Transcription Factor metabolism
Hematopoiesis drug effects
Hematopoietic Stem Cells drug effects
Humans
Male
Mice
Mice, Knockout
Mice, Transgenic
Proto-Oncogene Proteins c-myc metabolism
RNA, Messenger genetics
Reverse Transcriptase Polymerase Chain Reaction
Antigens, Neoplasm physiology
Bone Marrow metabolism
Gene Expression Regulation
Hematopoiesis physiology
Hematopoietic Stem Cells physiology
Proto-Oncogene Proteins c-myc genetics
RNA-Binding Proteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 117
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 21447833
- Full Text :
- https://doi.org/10.1182/blood-2010-12-325332