Biomedical subjects

Degeng Wang

Publications and source records attributed to Degeng Wang.

5 recordsLinked to original sources

PubMed2005

Examining the architecture of cellular computing through a comparative study with a computer.

The computer and the cell both use information embedded in simple coding, the binary software code and the quadruple genomic code, respectively, to support system operations. A comparative examination of their system architecture as well as their information storage and utilization schemes is performed. On top of the code, both systems display a modular, multi-layered architecture, which, in the case of a computer, arises from human engineering efforts through a combination of hardware implementation and software abstraction. Using the computer as a reference system, a simplistic mapping of the architectural components between the two is easily detected. This comparison also reveals that a cell abolishes the software-hardware barrier through genomic encoding for the constituents of the biochemical network, a cell's "hardware" equivalent to the computer central processing unit (CPU). The information loading (gene expression) process acts as a major determinant of the encoded constituent's abundance, which, in turn, often determines the "bandwidth" of a biochemical pathway. Cellular processes are implemented in biochemical pathways in parallel manners. In a computer, on the other hand, the software provides only instructions and data for the CPU. A process represents just sequentially ordered actions by the CPU and only virtual parallelism can be implemented through CPU time-sharing. Whereas process management in a computer may simply mean job scheduling, coordinating pathway bandwidth through the gene expression machinery represents a major process management scheme in a cell. In summary, a cell can be viewed as a super-parallel computer, which computes through controlled hardware composition. While we have, at best, a very fragmented understanding of cellular operation, we have a thorough understanding of the computer throughout the engineering process. The potential utilization of this knowledge to the benefit of systems biology is discussed.

Cell Physiological Phenomena↗

PubMed2003

Regulated subset of G1 growth-control genes in response to derepression by the Wnt pathway.

Pitx2 is a bicoid-related homeodomain factor that is required for effective cell type-specific proliferation directly activating a specific growth-regulating gene cyclin D2. Here, we report that Pitx2, in response to the Wntbeta-catenin pathway and growth signals, also can regulate c-Myc and cyclin D1. Investigation of molecular mechanisms required for Pitx2-dependent proliferation, in these cases, further supports a nuclear role for beta-catenin in preventing the histone deacetylase 1-dependent inhibitory functions of several DNA-binding transcriptional repressors, potentially including E2F4p130 pocket protein inhibitory complex, as well as lymphoid enhancer factor 1 and Pitx2, by dismissal of histone deacetylase 1 and loss of its enzymatic activity. Thus, beta-catenin plays a signal-integrating role in Wnt- and growth factor-dependent proliferation events in mammalian development by both derepressing several classes of repressors and by activating Pitx2, regulating the activity of several growth control genes.

Animals↗

PubMed2003

The PlantsP and PlantsT Functional Genomics Databases.

PlantsP and PlantsT allow users to quickly gain a global understanding of plant phosphoproteins and plant membrane transporters, respectively, from evolutionary relationships to biochemical function as well as a deep understanding of the molecular biology of individual genes and their products. As one database with two functionally different web interfaces, PlantsP and PlantsT are curated plant-specific databases that combine sequence-derived information with experimental functional-genomics data. PlantsP focuses on proteins involved in the phosphorylation process (i.e., kinases and phosphatases), whereas PlantsT focuses on membrane transport proteins. Experimentally, PlantsP provides a resource for information on a collection of T-DNA insertion mutants (knockouts) in each kinase and phosphatase, primarily in Arabidopsis thaliana, and PlantsT uniquely combines experimental data regarding mineral composition (derived from inductively coupled plasma atomic emission spectroscopy) of mutant and wild-type strains. Both databases provide extensive information on motifs and domains, detailed information contributed by individual experts in their respective fields, and descriptive information drawn directly from the literature. The databases incorporate a unique user annotation and review feature aimed at acquiring expert annotation directly from the plant biology community. PlantsP is available at http://plantsp.sdsc.edu and PlantsT is available at http://plantst.sdsc.edu.

Arabidopsis↗

PubMed2003

Systematic trans-genomic comparison of protein kinases between Arabidopsis and Saccharomyces cerevisiae.

The genome of the budding yeast (Saccharomyces cerevisiae) provides an important paradigm for transgenomic comparisons with other eukaryotic species. Here, we report a systematic comparison of the protein kinases of yeast (119 kinases) and a reference plant Arabidopsis (1,019 kinases). Using a whole-protein-based, hierarchical clustering approach, the complete set of protein kinases from both species were clustered. We validated our clustering by three observations: (a) clustering pattern of functional orthologs proven in genetic complementation experiments, (b) consistency with reported classifications of yeast kinases, and (c) consistency with the biochemical properties of those Arabidopsis kinases already experimentally characterized. The clustering pattern identified no overlap between yeast kinases and the receptor-like kinases (RLKs) of Arabidopsis. Ten more kinase families were found to be specific for one of the two species. Among them, the calcium-dependent protein kinase and phosphoenolpyruvate carboxylase kinase families are specific for plants, whereas the Ca(2+)/calmodulin-dependent protein kinase and provirus insertion in mouse-like kinase families were found only in yeast and animals. Three yeast kinase families, nitrogen permease reactivator/halotolerance-5), polyamine transport kinase, and negative regulator of sexual conjugation and meiosis, are absent in both plants and animals. The majority of yeast kinase families (21 of 26) display Arabidopsis counterparts, and all are mapped into Arabidopsis families of intracellular kinases that are not related to RLKs. Representatives from 11 of the common families (54 kinases from Arabidopsis and 17 from yeast) share an extremely high degree of similarity (blast E value < 10(-80)), suggesting the likelihood of orthologous functions. Selective expansion of yeast kinase families was observed in Arabidopsis. This is most evident for yeast genes CBK1, HRR25, and SNF1 and the kinase family S6K. Reduction of kinase families was also observed, as in the case of the NEK-like family. The distinguishing features between the two sets of kinases are the selective expansion of yeast families and the generation of a limited number of new kinase families for new functionality in Arabidopsis, most notably, the Arabidopsis RLKs that constitute important components of plant intercellular communication apparatus.

Arabidopsis↗

PubMed2002

Activation of the TGFalpha autocrine loop is downstream of IGF-I receptor activation during mitogenesis in growth factor dependent human colon carcinoma cells.

The inappropriate expression of TGFalpha in growth arrest contributes to malignant progression in human colon carcinoma cells. Early stage, non-progressed colon tumor cells show a down-regulation of TGFalpha in growth arrest and require both nutrients and growth factors for re-entry into the cell cycle. In contrast, highly progressed cells up-regulate TGFalpha during growth arrest and require only nutrients for re-entry. Given the importance of TGFalpha in malignant progression, this work addressed the regulation of TGFalpha expression in the early stage colon carcinoma cell line, FET. Growth-arrested FET cells down-regulated the expression of TGFalpha, EGFr and, in turn, EGFr activation. These quiescent cells continued to express high levels of IGF-IR protein, but IGF-IR activation was undetectable. Cell cycle re-entry required exogenous growth factor activation of the IGF-IR by insulin or IGF-I. This IGF-IR activation resulted in S phase re-entry and was accompanied by an approximate threefold induction of TGFalpha expression along with EGFr activation at 1 h following release from growth arrest. Activation of IGF-IR occurred within 5 min of cell-cycle re-entry. Previously identified DNA binding proteins which bind to a unique TGFalpha/EGF response element within the TGFalpha promoter were similarly induced following IGF-IR activation. The addition of EGFr neutralizing antibodies abolished the activated IGF-IR stimulated S phase re-entry. Moreover, disruption of the growth arrest associated down-regulation of TGFalpha in FET cells by constitutive TGFalpha expression abrogated the requirement for IGF-IR activation for cell cycle re-entry. Consequently, this study indicates, for the first time, that IGF-IR activation up-regulates components of the TGFalpha autocrine loop resulting in TGFalpha-mediated EGFr activation which was critical for IGF-IR mediated re-entry into the cell cycle from the growth-arrested state.

Cell Division↗