Differential-Effects of Viral and Cellular Oncogenes on the Growth Factor-Dependency of Hematopoietic-Cells

McCubrey, JA; Steelman, LS; Xy, Wang; Algate, Paul A.; Hoyle, Paul; White, Christine P.; Davidian, Ew; Prevost, Kd; Robbins, P; Mylott, D; Mk, White

doi:10.3892/ijo.7.2.295

Cited by 14 publications

(26 citation statements)

References 44 publications

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“…26,27 The pLNC⌬Raf-1:ER vector contains the catalytic domain of human Raf-1 (aa 305-648) fused to the human hormone binding (hb) domain of the estrogen receptor (ER). The ⌬Raf-1:ER chimeric protein requires ␤-estradiol for its activation.…”

Section: Retroviral Infection Of Cellsmentioning

confidence: 99%

“…The ⌬Raf-1:ER chimeric protein requires ␤-estradiol for its activation. 26 The pLNC⌬A-Raf:ER retroviral vector encodes the catalytic domain of murine ARaf fused to the hbER inserted into the pLNCX vector. 27 The plasmids encoding the Raf retroviruses were generously provided by Dr Martin McMahon (UCSF, San Francisco, CA, USA).…”

Section: Retroviral Infection Of Cellsmentioning

confidence: 99%

“…Immune complexes were collected, washed in lysis buffer, and the activities of ⌬Raf:ER proteins were assessed by incubation for 30 min at 30°C in a reaction mix containing 25 mM Hepes (pH 7.4), 10 mM MgCl 2 , 1 mM DTT, 50 M ATP and 10 M ␥-32 P-ATP (3000 C1/mmol; NEN) with 12.5 g of purified recombinant enzymatically unactive GST-MEK1 (Upstate Biotechnology (UBI), Lake Placid NY, USA) as a substrate as described previously. 14,[26][27][28][29][30] The reactions were analyzed by SDS-polyacrylamide gel electrophoresis and electrotransference to polyvinylidene difluoride membranes (PVDF, Immunobilon P; Millipore, Medford, MA, USA). Western blots were first exposed to X-ray film to quantitate GST-MEK1 phosphorylation and subsequently probed with an ␣-hbER Ab to quantitate the amount of the ⌬Raf:ER protein in each immunoprecipitate.…”

Section: Determination Of Raf Kinase Activitymentioning

confidence: 99%

“…1,21 Loss of Raf expression can have severe developmental consequences for the organism. [22][23][24][25][26][27][28][29] The Raf proteins have been dissected into three different functional domains: CR1, CR2, and CR3. The CR1 region has the binding site for an activated Ras protein.…”

Section: Introductionmentioning

confidence: 99%

“…1,21 The CR2 region negatively regulates the Raf kinase domain (CR3) which is located in the carboxyl terminal of Raf. [26][27][28][29][30][31] N-terminal-deleted forms of these Raf proteins result in constitutively activated oncoproteins which transform fibroblastic murine NIH-3T3 cells. [26][27][28] Certain virally encoded oncoproteins (v-Abl, v-Erb-B, vFms, v-Fps, v-Raf and v-Src), activated cellular oncoproteins (BCR-ABL, TEL-ABL, TEL-JAK), membrane growth factor receptors (epidermal growth factor receptor (EGF-R), insulinlike growth factor-1 receptor (IGF-1R), 1,[32][33][34][35] and specific protein kinase C isoforms 35 can alter the cytokine dependency of certain murine and human hematopoietic cells.…”

Section: Introductionmentioning

confidence: 99%

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Effects of deregulated Raf activation on integrin, cytokine-receptor expression and the induction of apoptosis in hematopoietic cells

Weinstein‐Oppenheimer

Steelman

Algate

et al. 2000

Leukemia

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The effects of deregulated Raf activation on the growth and differentiation of hematopoietic cells were investigated. The cytokine-dependent murine myeloid FDC-P1 and human erythroleukemic TF-1 cell lines were transformed to grow in response to deregulated Raf expression in the absence of exogenous cytokines. The conditionally active Raf proteins were regulated by ␤-estradiol as cDNAs containing the Raf catalytic, but lacking negative-regulatory domains, were ligated to the hormone binding domain of the estrogen receptor (⌬Raf:ER). Continuous ⌬Raf expression prevented apoptosis in the absence of exogenous cytokines and altered the morphology of the FD/⌬Raf:ER cells as they grew in large aggregated masses (Ͼ100 cells) whereas the parental cytokinedependent FDC-P1 cells grew in smaller grape-like clusters (Ͻ10 cells). FD/⌬Raf-1:ER cells growing in response to Raf activation displayed decreased levels of the Mac-2 and Mac-3 molecules on their cell surface. In contrast, when these cells were cultured in IL-3, higher levels of these adhesion molecules were detected. Expression of activated Raf oncoproteins also abrogated cytokine dependency and prevented apoptosis of TF-1 cells. Moreover, the differentiation status of these Raf-responsive cells was more immature upon Raf activation as culture with the differentiation-inducing agent phorbol 12 myristate 13-acetate (PMA) and ␤-estradiol resulted in decreased levels of the CD11b and CD18 integrin molecules on the cell surface. In contrast when the Raf-responsive cells were induced to differentiate with PMA and GM-CSF, in the absence of ⌬Raf:ER activation, increased levels of the CD11b and CD18 molecules were detected. Retinoic acid (RA) inhibited 3 H-thymidine incorporation in response to GM-CSF. Interestingly, Raf activation counterbalanced the inhibition of DNA synthesis caused by RA but not PMA. Thus deregulated Raf expression can alter cytokine dependency, integrin expression and the stage of differentiation. These Raf-responsive cell lines will be useful in elucidating the roles of the MAP kinase cascade on hematopoietic cell differentiation and malignant transformation. Leukemia

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Section: Retroviral Infection Of Cellsmentioning

confidence: 99%

Section: Retroviral Infection Of Cellsmentioning

confidence: 99%

Section: Determination Of Raf Kinase Activitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Effects of deregulated Raf activation on integrin, cytokine-receptor expression and the induction of apoptosis in hematopoietic cells

Weinstein‐Oppenheimer

Steelman

Algate

et al. 2000

Leukemia

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Interfering With Tumor Pathways That Augment Viral Oncolysis

Bell

2011

Molecular Therapy

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Characterization of proteins binding the 3′ regulatory region of the IL-3 gene in IL-3-dependent and autocrine-transformed hematopoietic cells

McCubrey

1998

Leukemia

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Previously we documented the prolongation of the IL-3 mRNA half-life in an autocrine-transformed cell line. This cell line has an intracisternal type A particle transposition in the IL-3 mRNA 3′ untranslated region which displaced four out of six AUUUA motifs involved in IL-3 mRNA destabilization. In this study, the proteins binding to the IL-3 mRNA AU-rich elements (ARE) were examined. Specific protein binding was detected to the wildtype IL-3 ARE region which contained 6 AUUUA motifs (AU 6 ). In contrast, no binding was detected to the mutated IL-3 ARE region which contained only two AUUUA motifs (AU 2 ). Proteins with apparent molecular weights of 36, 40, 43, 46, 55, 57, 68 and 95 kDa were bound to AU 6 motif. The hnRNP C and AUF-1 (hnRNP D) proteins were determined to be two of the IL-3 ARE binding proteins. Incubation of protein extracts with antibodies to hnRNP C and AUF-1 significantly decreased the protein binding to the IL-3 ARE. Treatment of IL-3 dependent cells with calcium ionophores eliminated the proteins binding to the ARE in wild-type IL-3-dependent FL5.12 cells and also resulted in the accumulation of IL-3 mRNA transcripts with a long half-life. These results indicated that there was a specific complex which bound the IL-3 mRNA 3′ ARE. Mutations which truncate the IL-3 ARE eliminate the ability of proteins to bind this regulatory region and can result in autocrine transformation due to the presence of IL-3 mRNA transcripts with a long half-life.

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Differential-Effects of Viral and Cellular Oncogenes on the Growth Factor-Dependency of Hematopoietic-Cells

Cited by 14 publications

References 44 publications

Effects of deregulated Raf activation on integrin, cytokine-receptor expression and the induction of apoptosis in hematopoietic cells

Effects of deregulated Raf activation on integrin, cytokine-receptor expression and the induction of apoptosis in hematopoietic cells

Interfering With Tumor Pathways That Augment Viral Oncolysis

Characterization of proteins binding the 3′ regulatory region of the IL-3 gene in IL-3-dependent and autocrine-transformed hematopoietic cells

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