Proteomic analysis of transcription factor interactions in myeloid stem cell development and leukaemia

Behre, Gerhard; Reddy, Venkateshwar A.; Tenen, Daniel G.; Hiddemann, Wolfgang; Zada, Abdul Ali Peer; Singh, Sheo Mohan

doi:10.1517/14728222.6.4.491

Cited by 14 publications

(4 citation statements)

References 11 publications

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“…65 The use of approaches of functional genomics and proteomics has allowed the discovery of new proteins involved in the origin of the neoplasia and their participation in the development of the disease. Emerging studies have identified the changes in the proteasome associated with the action of Bcr-Abl tyrosine kinases in chronic myeloid leukemia, 66 protein targets of transcription factors involved in myeloid stem cell development and leukemia, 67 or new protein …”

Section: Proteomic Approaches To the Altered Expression Of Tf And Vegmentioning

confidence: 99%

Tissue factor as an effector of angiogenesis and tumor progression in hematological malignancies

et al. 2006

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Section: Proteomic Approaches To the Altered Expression Of Tf And Vegmentioning

confidence: 99%

Tissue factor as an effector of angiogenesis and tumor progression in hematological malignancies

et al. 2006

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“…Potential antagonistic protein interactions leading to a block in C/EBPa function in AML have been well implicated in recent findings (Pabst et al, 2001a;Vangala et al, 2003;Zheng et al, 2004). Interestingly, C/EBPa also functions via direct proteinprotein interactions in normal stem cell development (Behre et al, 2002a;D'Alo et al, 2003;Muller et al, 2004); PU.1 and c-Jun inactivation (Rangatia et al, 2002;Reddy et al, 2002), E2F repression (Porse et al, 2001), and cdk2 and cdk4 inhibition (Wang et al, 2001) by C/EBPa are all accompanied by direct protein-protein interactions. Moreover, different protein partners of C/EBPa in young and old mice livers itself demonstrate the importance of protein-protein interactions during ageing (Iakova et al, 2003).…”

Section: Introductionmentioning

confidence: 97%

Proteomic identification of C/EBP-DBD multiprotein complex: JNK1 activates stem cell regulator C/EBPα by inhibiting its ubiquitination

et al. 2006

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Functional inactivation of transcription factors in hematopoietic stem cell development is involved in the pathogenesis of acute myeloid leukemia (AML). Stem cell regulator C/enhancer binding protein (EBP)a is among such transcription factors known to be inactive in AML. This is either due to mutations or inhibition by protein-protein interactions. Here, we applied a mass spectrometry-based proteomic approach to systematically identify putative co-activator proteins interacting with the DNA-binding domain (DBD) of C/EBP transcription factors. In our proteomic screen, we identified c-Jun N-terminal kinase (JNK) 1 among others such as PAK6, MADP-1, calmodulin-like skin proteins and ZNF45 as proteins interacting with DBD of C/EBPs from nuclear extract of myelomonocytic U937 cells. We show that kinase JNK1 physically interacts with DBD of C/EBPa in vitro and in vivo. Furthermore, we show that active JNK1 inhibits ubiquitination of C/EBPa possibly by phosphorylating in its DBD. Consequently, JNK1 prolongs C/EBPa protein half-life leading to its enhanced transactivation and DNA-binding capacity. In certain AML patients, however, the JNK1 mRNA expression and its kinase activity is decreased which suggests a possible reason for C/EBPa inactivation in AML. Thus, we report the first proteomic screen of C/EBP-interacting proteins, which identifies JNK1 as positive regulator of C/EBPa.

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“…Most of the proteomics experiments with time frames longer than 24 h explore the long-term transformations of cells [95,96]. These effects may be related to cells of a selected type, e.g., exploring the differentiation of cells, or to cells in a context of multicellular organisms, e.g., the study of cells in a developing body.…”

Section: Dynamics Of Proteomesmentioning

confidence: 99%

“…These effects may be related to cells of a selected type, e.g., exploring the differentiation of cells, or to cells in a context of multicellular organisms, e.g., the study of cells in a developing body. This includes the profiling of various tissues and different cell lines that originate from the same tissue [95,96]. Thus, longer time frames in proteomics studies are associated with the larger complexity of the studied system (Fig.…”

Section: Dynamics Of Proteomesmentioning

confidence: 99%

Bridging proteomics and systems biology: What are the roads to be traveled?

Souchelnytskyi

2005

Proteomics

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The comprehensive study of proteomes has become an important part of attempts to uncover the systemic properties of biological systems. Proteomics provides data of a quality which increasingly fulfills strict requirements of systems biology for quantitative and qualitative information. Notably, proteomics can generate rich datasets that describe dynamic changes of proteomes. On the other hand, large-scale modeling requires the development of mathematic tools that are adequate for the processing of largely uncertain biological data. In this review, recent developments that pave the way for the integration of proteomics into systems biology are discussed. These developments include the standardization of data acquisition and presentation, the increased comprehensiveness of proteomics studies in description of functional status, localization and dynamics of proteins, and advanced modeling approaches. Proteomics and modeling of biological processesThe dynamic complexity of biological processes has been less well understood, when compared to many physical and chemical processes. Apparently, sending a man to the Moon is less complicated than the full understanding of how bruises heal. This situation is about to change: the sequencing of a number of genomes, large-scale explorations of transcriptomes, proteomes and metabolomes, and a huge volume of directed studies inspire hope that we will be able to describe a living creature in the strict language of mathematics. Most importantly, there is a hope that we will be able to design better treatments and predict outcomes for human diseases. The development of modeling tools fuels these expectations, with the dawn of systems biology. Study of the systemic properties of biological systems, as systems biology can be defined, has already provided successful examples, e.g., insights into the physiology of the heart, diabetes, asthma and cancer (reviewed in [1,2]).Building and analysis of models of biological processes comprises a number of modeling tools, and addresses biological complexity on the levels from biochemical reactions and cell physiology to behavior and evolution [3,4]. Here and through-out this review the term "model" refers to description of biological processes in mathematical terms, without discrimination of mathematical tools. Consequently, modeling is defined as "the application of methods to analyze complex, real-world problems to make predictions about what might happen with various actions" (see Computational Science Glossary, wofford.info/ecs/glossary/ terms.htm; Table 1). Modeling tools cover a broad range of mathematical methods, from systems of differential equations to statistical correlation tools [3,4]. Some of the tools require detailed knowledge about components, e.g., to build a systems of differential equations for modeling of a signaling Abbreviations: ABPP, activity-based proteome profiling; BEMAD, b-elimination followed by Michael addition with DTT; FAK, focal adhesion kinase; FRET, fluorescence resonance energy transfer; GFP, green fluores...

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Proteomic analysis of transcription factor interactions in myeloid stem cell development and leukaemia

Cited by 14 publications

References 11 publications

Tissue factor as an effector of angiogenesis and tumor progression in hematological malignancies

Tissue factor as an effector of angiogenesis and tumor progression in hematological malignancies

Proteomic identification of C/EBP-DBD multiprotein complex: JNK1 activates stem cell regulator C/EBPα by inhibiting its ubiquitination

Bridging proteomics and systems biology: What are the roads to be traveled?

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