scholarly journals Ability of the Activated PI3K/Akt Oncoproteins to Synergize with MEK1 and Induce Cell Cycle Progression and Abrogate the Cytokine-Dependence of Hematopoietic Cells

Cell Cycle ◽  
2004 ◽  
Vol 3 (4) ◽  
pp. 501-510 ◽  
Author(s):  
John G. Shelton ◽  
William L. Blalock ◽  
Edmond R. White ◽  
Linda S. Steelman ◽  
James A McCubrey
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Hematopoietic Cells ◽  
Cycle Progression ◽  
Induce Cell Cycle Progression

Homing efficiency, cell cycle kinetics, and survival of quiescent and cycling human CD34+ cells transplanted into conditioned NOD/SCID recipients

Blood ◽  
2002 ◽  
Vol 99 (5) ◽  
pp. 1585-1593 ◽  
Author(s):  
Anna Jetmore ◽  
P. Artur Plett ◽  
Xia Tong ◽  
Frances M. Wolber ◽  
Robert Breese ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Hematopoietic Cells ◽  
Cycle Progression ◽  
Hematopoietic Stem ◽  
Human Cd34 ◽  
Nonobese Diabetic ◽  
Cd34 Cells ◽  
G1 Cells ◽  
Active Proliferation

Differences in engraftment potential of hematopoietic stem cells (HSCs) in distinct phases of cell cycle may result from the inability of cycling cells to home to the bone marrow (BM) and may be influenced by the rate of entry of BM-homed HSCs into cell cycle. Alternatively, preferential apoptosis of cycling cells may contribute to their low engraftment potential. This study examined homing, cell cycle progression, and survival of human hematopoietic cells transplanted into nonobese diabetic severe combined immunodeficient (NOD/SCID) recipients. At 40 hours after transplantation (AT), only 1% of CD34+ cells, or their G0(G0CD34+) or G1(G1CD34+) subfractions, was detected in the BM of recipient mice, suggesting that homing of engrafting cells to the BM was not specific. BM of NOD/SCID mice receiving grafts containing approximately 50% CD34+ cells harbored similar numbers of CD34+ and CD34− cells, indicating that CD34+ cells did not preferentially traffic to the BM. Although more than 64% of human hematopoietic cells cycled in culture at 40 hours, more than 92% of cells recovered from NOD/SCID marrow were quiescent. Interestingly, more apoptotic human cells were detected at 40 hours AT in the BM of mice that received xenografts of expanded cells in S/G2+M than in recipients of G0/G1 cells (34.6% ± 5.9% and 17.1% ± 6.3%, respectively; P < .01). These results suggest that active proliferation inhibition in the BM of irradiated recipients maintains mitotic quiescence of transplanted HSCs early AT and may trigger apoptosis of cycling cells. These data also illustrate that trafficking of transplanted cells to the BM is not selective, but lodgment of BM-homed cells may be specific.

scholarly journals Cyclin E and Bcl-xL cooperatively induce cell cycle progression in c-Rel−/− B cells

Oncogene ◽  
2003 ◽  
Vol 22 (52) ◽  
pp. 8472-8486 ◽  
Author(s):  
Shuhua Cheng ◽  
Constance Yu Hsia ◽  
Gustavo Leone ◽  
Hsiou-Chi Liou
Keyword(s):  
Cell Cycle ◽  
B Cells ◽  
Cell Cycle Progression ◽  
Cyclin E ◽  
Cycle Progression ◽  
Induce Cell Cycle Progression

scholarly journals B-Raf and Insulin Synergistically Prevent Apoptosis and Induce Cell Cycle Progression in Hematopoietic Cell

Cell Cycle ◽  
2004 ◽  
Vol 3 (2) ◽  
pp. 184-191 ◽  
Author(s):  
John G. Shelton ◽  
Fumin Chang ◽  
John T. Lee ◽  
Richard A. Franklin ◽  
Linda S. Steelman ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Hematopoietic Cell ◽  
Cycle Progression ◽  
Induce Cell Cycle Progression

scholarly journals Synergy between PI3K/Akt and Raf/MEK/ERK Pathways in IGF-1R Mediated Cell Cycle Progression and Prevention of Apoptosis in Hematopoietic Cells

Cell Cycle ◽  
2004 ◽  
Vol 3 (3) ◽  
pp. 370-377 ◽  
Author(s):  
John G. Shelton ◽  
Linda S. Steelman ◽  
Edmond R. White ◽  
James A McCubrey
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Hematopoietic Cells ◽  
Cycle Progression

scholarly journals BCR targets cyclin D2 via Btk and the p85α subunit of PI3-K to induce cell cycle progression in primary mouse B cells

Oncogene ◽  
2003 ◽  
Vol 22 (15) ◽  
pp. 2248-2259 ◽  
Author(s):  
Janet Glassford ◽  
Inês Soeiro ◽  
Sara M Skarell ◽  
Lolita Banerji ◽  
Mary Holman ◽  
...  
Keyword(s):  
Cell Cycle ◽  
B Cells ◽  
Cell Cycle Progression ◽  
Cyclin D2 ◽  
Cycle Progression ◽  
Primary Mouse ◽  
Induce Cell Cycle Progression

scholarly journals Raf-Induced Cell Cycle Progression in Human TF-1 Hematopoietic Cells

Cell Cycle ◽  
2002 ◽  
Vol 1 (3) ◽  
pp. 218-224 ◽  
Author(s):  
Fumin Chang ◽  
Linda S. Steelman ◽  
James A McCubrey
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Hematopoietic Cells ◽  
Cycle Progression

Phosphorylation of Runx1 by Cyclin-Dependent Kinases Regulates Its Interaction with HDAC1 and HDAC3.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1381-1381 ◽  
Author(s):  
Hong Guo ◽  
Alan D. Friedman
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Hematopoietic Cells ◽  
Cyclin D3 ◽  
Mrna Levels ◽  
Cycle Progression ◽  
Hematopoietic Stem ◽  
Protein Levels ◽  
Cdk Phosphorylation ◽  
Regulation Of Cell Cycle

Abstract Runx1/AML1 is a key regulator of hematopoiesis and leukemic transformation, as RUNX1(−/−) mice do not develop definitive hematopoietic stem cells, and sever alleukemic oncogenes, e.g. AML1-ETO, CBFβ-SMMHC, or TEL-AML1, inhibit Runx1activities. We have investigated regulation of cell cycle progression by Runx1. Runx1stimulates G1 to S cell cycle progression in hematopoietic cell lines and in transduced myeloid progenitors, and inhibition of Runx1 by CBFβ-SMMHC or AML1-ETO slows G1 progression. Runx1 induces cdk4 and cyclin D3 transcription, and exogenous cdk4, cyclin D2, or c-Myc overcomes inhibition of G1 progression by CBF oncoproteins. In addition to regulating cell cycle progression, Runx1 protein levels are themselves increased as hematopoietic cells progress from G1 to S to G2/M, though mRNA levels remain constant. Runx1 contains three consensus cdk sites, (S/T)PX(R/K), S48, S303, and S424, and using phospho-specific antisera we find that each of these is modified in hematopoietic cells. Mutation of these serines to aspartic acid, mimicking phosphorylation, increases trans-activation of a reporter containing four CBF sites or the TCRβ promoter, whereas mutation to alanine reduces trans-activation. p300 interacts similarly with Runx1(tripleA) and Runx1(tripleD). We have now evaluated interaction of HDACs1–8 with these variants and Runx1 and find that both HDAC1 and HDAC3 have reduced affinity for RUNX1(tripleD), as assessed by co-immunoprecipitation from transiently transfected 293T cells. Evaluation of single serine residue mutants (S48D, S303D, and S424D) demonstrates reduced affinity of HDAC1 or HDAC3 specifically for the Runx1(S424D) mutant, consistent with previous mapping of the Runx1:HDAC1 and Runx1:HDAC3 interactions to this region of Runx1. Thus, cdk phosphorylation of Runx1 S424 reduces affinity for HDAC1 and HDAC3, increasing Runx1 trans-activation potency. Regulation of Runx1 activity by cdks may control key developmental processes, including expansion of definitive HSC during development and regulation of the balance between adult HSC quiescence and proliferation.

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