THE FATE OF CD34- HEMATOPOIETIC PROGENITOR CELLS IN DIFFERENTIATION AND PROLIFERATION IS DEPENDENT UPON GROWTH FACTOR INDUCED EXPRESSION OF p27kip-1 AS THE CHECKPOINT OF CELL CYCLE PROGRESSION

ABSTRACT E2F plays critical roles in cell cycle progression by regulating the expression of genes involved in nucleotide synthesis, DNA replication, and cell cycle control. We show that the combined loss of E2F1 and E2F2 in mice leads to profound cell-autonomous defects in the hematopoietic development of multiple cell lineages. E2F2 mutant mice show erythroid maturation defects that are comparable with those observed in patients with megaloblastic anemia. Importantly, hematopoietic defects observed in E2F1/E2F2 double-knockout (DKO) mice appear to result from impeded S phase progression in hematopoietic progenitor cells. During DKO B-cell maturation, differentiation beyond the large pre-BII-cell stage is defective, presumably due to failed cell cycle exit, and the cells undergo apoptosis. However, apoptosis appears to be the consequence of failed maturation, not the cause. Despite the accumulation of hematopoietic progenitor cells in S phase, the combined loss of E2F1 and E2F2 results in significantly decreased expression and activities of several E2F target genes including cyclin A2. Our results indicate specific roles for E2F1 and E2F2 in the induction of E2F target genes, which contribute to efficient expansion and maturation of hematopoietic progenitor cells. Thus, E2F1 and E2F2 play essential and redundant roles in the proper coordination of cell cycle progression with differentiation which is necessary for efficient hematopoiesis.

Download Full-text

H4 Histamine Receptors Mediate Cell Cycle Arrest in Growth Factor-Induced Murine and Human Hematopoietic Progenitor Cells

PLoS ONE ◽

10.1371/journal.pone.0006504 ◽

2009 ◽

Vol 4 (8) ◽

pp. e6504 ◽

Cited By ~ 21

Author(s):

Anne-France Petit-Bertron ◽

François Machavoine ◽

Marie Paule Defresne ◽

Michel Gillard ◽

Pierre Chatelain ◽

...

Keyword(s):

Cell Cycle ◽

Growth Factor ◽

Cell Cycle Arrest ◽

Progenitor Cells ◽

Histamine Receptors ◽

Hematopoietic Progenitor Cells ◽

Hematopoietic Progenitor ◽

Cycle Arrest ◽

Mediate Cell

Download Full-text

FoxM1 Regulates Growth Factor-induced Expression of Kinase-interacting Stathmin (KIS) to Promote Cell Cycle Progression

Journal of Biological Chemistry ◽

10.1074/jbc.m705792200 ◽

2007 ◽

Vol 283 (1) ◽

pp. 453-460 ◽

Cited By ~ 41

Author(s):

Vladimir Petrovic ◽

Robert H. Costa ◽

Lester F. Lau ◽

Pradip Raychaudhuri ◽

Angela L. Tyner

Keyword(s):

Cell Cycle ◽

Growth Factor ◽

Cell Cycle Progression ◽

Cycle Progression ◽

Induced Expression ◽

Promote Cell Cycle Progression

Download Full-text

Cytosolic Ca2+ transients are not required for platelet-derived growth factor to induce cell cycle progression of vascular smooth muscle cells in primary culture. Actions of tyrosine kinase.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)37069-2 ◽

1994 ◽

Vol 269 (12) ◽

pp. 9011-9018

Author(s):

S. Kobayashi ◽

J. Nishimura ◽

H. Kanaide

Keyword(s):

Cell Cycle ◽

Smooth Muscle ◽

Growth Factor ◽

Smooth Muscle Cells ◽

Primary Culture ◽

Vascular Smooth Muscle Cells ◽

Cell Cycle Progression ◽

Platelet Derived Growth Factor ◽

Cycle Progression ◽

Induce Cell Cycle Progression

Download Full-text

Insulin-like Growth Factor-I Extendsin VitroReplicative Life Span of Skeletal Muscle Satellite Cells by Enhancing G1/S Cell Cycle Progression via the Activation of Phosphatidylinositol 3′-Kinase/Akt Signaling Pathway

Journal of Biological Chemistry ◽

10.1074/jbc.m005832200 ◽

2000 ◽

Vol 275 (46) ◽

pp. 35942-35952 ◽

Cited By ~ 154

Author(s):

Manu V. Chakravarthy ◽

Tsghe W. Abraha ◽

Robert J. Schwartz ◽

Marta L. Fiorotto ◽

Frank W. Booth

Keyword(s):

Cell Cycle ◽

Skeletal Muscle ◽

Growth Factor ◽

Satellite Cells ◽

Cell Cycle Progression ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Phosphatidylinositol 3 Kinase ◽

Cycle Progression ◽

Factor I

Download Full-text

Regulation of Raf-1-dependent signaling during early Xenopus development.

Molecular and Cellular Biology ◽

10.1128/mcb.15.12.6686 ◽

1995 ◽

Vol 15 (12) ◽

pp. 6686-6693 ◽

Cited By ~ 21

Author(s):

A M MacNicol ◽

A J Muslin ◽

E L Howard ◽

A Kikuchi ◽

M C MacNicol ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Progression ◽

Mapk Pathway ◽

Mapk Signaling ◽

Embryonic Cell ◽

Cycle Progression ◽

Mapk Activity ◽

Cytostatic Factor ◽

Differentiation And Proliferation

The Raf-1 gene product is activated in response to cellular stimulation by a variety of growth factors and hormones. Raf-1 activity has been implicated in both cellular differentiation and proliferation. We have examined the regulation of the Raf-1/MEK/MAP kinase (MAPK) pathway during embryonic development in the frog Xenopus laevis. We report that Raf-1, MEK, and MAPK activities are turned off following fertilization and remain undetectable up until blastula stages (stage 8), some 4 h later. Tight regulation of the Raf-1/MEK/MAPK pathway following fertilization is crucial for embryonic cell cycle progression. Inappropriate reactivation of MAPK activity by microinjection of oncogenic Raf-1 RNA results in metaphase cell cycle arrest and, consequently, embryonic lethality. Our findings demonstrate an absolute requirement, in vivo, for inactivation of the MAPK signaling pathway to allow normal cell cycle progression during the period of synchronous cell divisions which occur following fertilization. Further, we show that cytostatic factor effects are mediated through MEK and MAPK.

Download Full-text