Cyclin A and the retinoblastoma gene product complex with a common transcription factor

Nature ◽  
1991 ◽  
Vol 352 (6332) ◽  
pp. 249-251 ◽  
Author(s):  
Lasantha R. Bandara ◽  
Jörg P. Adamczewski ◽  
Tim Hunt ◽  
Nicholas B. La Thangue
Keyword(s):  
Transcription Factor ◽  
Gene Product ◽  
Cyclin A ◽  
Retinoblastoma Gene ◽  
Common Transcription Factor ◽  
Retinoblastoma Gene Product

Retinoblastoma gene product activates expression of the human TGF-β2 gene through transcription factor ATF-2

Nature ◽  
1992 ◽  
Vol 358 (6384) ◽  
pp. 331-334 ◽  
Author(s):  
Seong-Jin Kim ◽  
Susanne Wagner ◽  
Fang Liu ◽  
Michael A. O'Reilly ◽  
Paul D. Robbins ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Gene Product ◽  
Retinoblastoma Gene ◽  
Retinoblastoma Gene Product

Identification of distinct roles for separate E1A domains in disruption of E2F complexes

1993 ◽  
Vol 13 (11) ◽  
pp. 7029-7035
Author(s):  
M A Ikeda ◽  
J R Nevins
Keyword(s):  
Transcription Factor ◽  
Gene Product ◽  
Protein Complexes ◽  
Cyclin A ◽  
Regulatory Proteins ◽  
Retinoblastoma Gene ◽  
Adenovirus E1a ◽  
E2f Transcription Factor ◽  
Cdk2 Complex ◽  
Equilibrium Dissociation

The adenovirus E1A protein can disrupt protein complexes containing the E2F transcription factor in association with cellular regulatory proteins such as the retinoblastoma gene product (Rb) and the Rb-related p107 protein. Previous experiments have shown that the CR1 and CR2 domains of E1A are required for this activity. We now demonstrate that the CR2 domain is essential for allowing E1A to interact with the E2F-Rb or the E2F-p107-cyclin A-cdk2 complex. Multimeric complexes containing E1A can be detected when the CR1 domain has been rendered inactive by mutation. In addition, the E1A CR1 domain, but not the CR2 domain, is sufficient to prevent the interaction of E2F with Rb or p107. On the basis of these results, we suggest a model whereby the CR2 domain brings E1A to the E2F complexes and then, upon a normal equilibrium dissociation of Rb or p107 from E2F, the E1A CR1 domain is able to block the site of interaction on Rb or p107, thereby preventing the re-formation of the complexes.

scholarly journals Identification of distinct roles for separate E1A domains in disruption of E2F complexes.

1993 ◽  
Vol 13 (11) ◽  
pp. 7029-7035 ◽  
Author(s):  
M A Ikeda ◽  
J R Nevins
Keyword(s):  
Transcription Factor ◽  
Gene Product ◽  
Protein Complexes ◽  
Cyclin A ◽  
Regulatory Proteins ◽  
Retinoblastoma Gene ◽  
Adenovirus E1a ◽  
E2f Transcription Factor ◽  
Cdk2 Complex ◽  
Equilibrium Dissociation

The adenovirus E1A protein can disrupt protein complexes containing the E2F transcription factor in association with cellular regulatory proteins such as the retinoblastoma gene product (Rb) and the Rb-related p107 protein. Previous experiments have shown that the CR1 and CR2 domains of E1A are required for this activity. We now demonstrate that the CR2 domain is essential for allowing E1A to interact with the E2F-Rb or the E2F-p107-cyclin A-cdk2 complex. Multimeric complexes containing E1A can be detected when the CR1 domain has been rendered inactive by mutation. In addition, the E1A CR1 domain, but not the CR2 domain, is sufficient to prevent the interaction of E2F with Rb or p107. On the basis of these results, we suggest a model whereby the CR2 domain brings E1A to the E2F complexes and then, upon a normal equilibrium dissociation of Rb or p107 from E2F, the E1A CR1 domain is able to block the site of interaction on Rb or p107, thereby preventing the re-formation of the complexes.

Stem-cell factor regulates the expression of cyclin A and retinoblastoma gene product in the growth and differentiation pathway of human megakaryocytic cells

1996 ◽  
Vol 122 (8) ◽  
pp. 445-452 ◽  
Author(s):  
Eiji Shimizu ◽  
Yasutake Takahashi ◽  
Akinori Shinohara ◽  
Yoshihiko Yamamoto ◽  
Seiji Yoshida ◽  
...  
Keyword(s):  
Stem Cell ◽  
Gene Product ◽  
Stem Cell Factor ◽  
Cyclin A ◽  
Retinoblastoma Gene ◽  
Retinoblastoma Gene Product

scholarly journals Control of Cell Cycle Progression in Human Natural Killer Cells Through Redox Regulation of Expression and Phosphorylation of Retinoblastoma Gene Product Protein

Blood ◽  
1997 ◽  
Vol 89 (11) ◽  
pp. 4092-4099 ◽  
Author(s):  
Akira Yamauchi ◽  
Eda T. Bloom
Keyword(s):  
Cell Cycle ◽  
Nk Cells ◽  
Natural Killer ◽  
Gene Product ◽  
Redox Regulation ◽  
Interleukin 2 ◽  
Retinoblastoma Gene ◽  
Regulation Of Expression ◽  
Retinoblastoma Gene Product

Abstract Using thiol deprivation, we have previously shown that the response of natural killer (NK) cells to interleukin-2 (IL-2) is subject to redox regulation downstream of IL-2 binding and internalization. We have now used the IL-2–dependent cell line, NK3.3 to study redox regulation of NK cells further, and found that NK3.3 cells neither incorporated [3H]-thymidine nor completed the G1-S phase transition in medium lacking the thiol-related compounds, L-cystine, and glutathione, despite the presence of sufficient IL-2. Thiol deprivation did not alter the induction of DNA interferon-γ activated sequence (GAS)-binding activity in response to IL-2. However, the retinoblastoma gene product (RB), a cyclin-dependent kinase (CDK) substrate, was phosphorylated within 24 hours after IL-2 stimulation in standard medium, but its expression and phosphorylation were reduced in thiol-depleted medium in both NK3.3 cells and freshly isolated NK cells. These reductions were not associated with an increased level of p27Kip1, an inhibitor of CDKs CDK6/2 in association with G1 cyclins. Reducing agents, N-acetylcysteine, reduced glutathione or 2-ME restored both RB phosphorylation and DNA synthesis in thiol-deprived NK3.3 cells. The in vitro kinase activities of CDK6 and CDK2 were prematurely increased by thiol deprivation. This enhancement was associated with CDK hyperphosphorylation and prolonged phosphorylation, and could be observed before and beyond IL-2 stimulation. The data suggest the possibility that the premature and prolonged enhancement of CDK activity in thiol-deprived NK cells is associated with, and therefore may contribute to, the reduced expression and phosphorylation of RB, and the associated cell cycle arrest.

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