Preliminary results indicate that the method can be extended to data sets representing short term drug action, such as phosphoproteomic data. Future research has to evaluate it`s applicability to data sets reflecting long-term response, such as transcriptomics or epigenetics data. However, more advanced mathematical methods may be able to overcome the abovementioned limitations of the meso-scale approach. Earlier results indicate options for Potassium phosphate monobasic extension towards heterogeneous data sets. In conclusion, our approach led to the identification of direct and indirect drug effects in a well-defined model system and should be amendable to various new drugs. Therefore, combination of broad proteome profiling and meso scale network reengineering provides a versatile tool to map a drug��s direct and indirect target pathways in a single set of experiments. Because of it`s adaptability to other model senarios, this approach should prove valuable at various stages of drug discovery as well as in translational studies of drug action in patient tissues. It represents a powerful method allowing the identification and assessment of multiple MoA using only unbiased protein expression data. Therefore it could contribute significantly to the drug discovery process of compounds acting via complex biological mechanisms. LIM-homeodomain class transcription factors are found in both vertebrates and invertebrates. These gene regulatory proteins are essential components of developmental programs in tissue and organ formation. In mammals, there are twelve genes encoding LIM-HD factors that share a similar protein domain structure featuring an amino terminus containing two LIM domains, a central homeodomain, followed by a carboxyl terminus of varying length. The LIM domains are zinc-coordinated structures that mediate interactions with other proteins and intramolecular contacts that affect protein function. The HD is a helical structure that forms the major DNA-binding interface. LIM-HD proteins have a characteristic HD amino acid sequence that establishes them as a specific subgroup of the large homeodomain family of transcription factors. Although it is clear that LIM-HD factors play essential roles in the determination and differentiation events that guide mammalian cell type specification, little is known about the mechanisms by which LIM-HD proteins and their cofactors regulate target gene transcription. The LIM-homeodomain 3 factor has critical roles in nervous system and pituitary gland development in mammals. In the anterior pituitary, LHX3 is required for four of the five hormone-producing cell types: somatotropes, lactotropes, gonadotropes and thyrotropes. These specialized cells produce hormones that regulate linear growth, reproduction and metabolism. In the nervous system LHX3 has defined roles in the specification of interneuron and motor neuron PPY A sub-types. Inactivating mutations in the human LHX3 gene typically lead to syndromic combined pituitary hormone deficiency diseases in pediatric patients that feature anterior pituitary hormone deficiencies and nervous system deficits, including deafness, developmental delay and a limited ability to rotate the neck.
With resistance to various anti-cancer drugs and irradiation
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