ORCID Profile
0000-0003-2057-9892
Current Organisation
Vanderbilt University Medical Center
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Publisher: The Endocrine Society
Date: 2001
Abstract: The androgen receptor (AR), a member of the steroid receptor superfamily of nuclear transcription factors, mediates androgen signaling in erse target tissues. Here we report AR gene mutations identified in human prostate cancer and the autochthonous transgenic adenocarcinoma of the mouse prostate model that colocate to residues (668)QPIF(671) at the boundary of the hinge and ligand-binding domain, resulting in receptors that exhibit 2- to 4-fold increased activity compared with wild-type AR in response to dihydrotestosterone, estradiol, progesterone, adrenal androgens, and the AR antagonist, hydroxyflutamide, without an apparent effect on receptor levels, ligand binding kinetics, or DNA binding. The expression of these or similar variants could explain the emergence of hormone refractory disease in a subset of patients. Homology modeling indicates that amino acid residues (668)QPIF(671) form a ridge bordering a potential protein-protein interaction surface. The naturally occurring AR gene mutations reported in this study result in decreased hydrophobicity of this surface, suggesting that altered receptor-protein interaction mediates the precocious activity of the AR variants.
Publisher: S. Karger AG
Date: 2006
DOI: 10.1159/000096630
Abstract: In recent years, considerable scientific interest has been devoted to amino acid supplementation and its role in regulating skeletal muscle metabolism in health, ageing and disease. This interest has, in part, stemmed from clinical evidence that traditional nutritional supplementation in patients is largely ineffective. In particular, this knowledge has prompted extensive research into the mechanisms responsible for amino acid stimulation of muscle protein metabolism in older adults with sarcopenia. It is well established that ageing diminishes muscle strength and size, contributing to a number of serious health problems such as an increased risk of falls and fractures. Although the reasons behind age-related sarcopenia are multifactorial and involve a complex interplay of hormonal and metabolic stimuli, it is clear that inadequate nutrition and inactivity are strong causative factors. Recently, the idea that elderly muscle is perhaps less anabolically sensitive to amino acids has been put forward as an additional causative factor. In light of this recent evidence, and the further suggestion that the effects of essential amino acids on skeletal muscle are independent of changes in insulin, newer studies are focusing on tailoring the optimal amount and proportion of amino acids needed to stimulate muscle protein synthesis most efficiently in ageing populations. Understanding the mechanisms of amino acid stimulation of muscle protein synthesis may also provide insight into the metabolic regulation of anabolism in skeletal muscle by key hormones such as growth hormone. In this article, we summarize current research concerning amino acids and skeletal muscle, particularly with regard to ageing and inactivity.
Publisher: Proceedings of the National Academy of Sciences
Date: 11-04-1995
Abstract: Progress toward understanding the biology of prostate cancer has been slow due to the few animal research models available to study the spectrum of this uniquely human disease. To develop an animal model for prostate cancer, several lines of transgenic mice were generated by using the prostate-specific rat probasin promoter to derive expression of the simian virus 40 large tumor antigen-coding region. Mice expressing high levels of the transgene display progressive forms of prostatic disease that histologically resemble human prostate cancer, ranging from mild intraepithelial hyperplasia to large multinodular malignant neoplasia. Prostate tumors have been detected specifically in the prostate as early as 10 weeks of age. Immunohistochemical analysis of tumor tissue has demonstrated that dorsolateral prostate-specific secretory proteins were confined to well-differentiated ductal epithelial cells adjacent to, or within, the poorly differentiated tumor mass. Prostate tumors in the mice also display elevated levels of nuclear p53 and a decreased heterogeneous pattern of androgen-receptor expression, as observed in advanced human prostate cancer. The establishment of breeding lines of transgenic mice that reproducibly develop prostate cancer provides an animal model system to study the molecular basis of transformation of normal prostatic cells and the factors influencing the progression to metastatic prostate cancer.
Publisher: Elsevier BV
Date: 05-2018
Publisher: American Association for Cancer Research (AACR)
Date: 07-2014
DOI: 10.1158/1541-7786.MCR-13-0611
Abstract: Protein–protein interactions (PPI) are a hallmark of cellular signaling. Such interactions occur abundantly within the cellular milieu and encompass interactions involved in vital cellular processes. Understanding the various types, mechanisms, and consequences of PPIs with respect to cellular signaling and function is vital for targeted drug therapy. Various types of small-molecule drugs and targeted approaches to drug design have been developed to modulate PPIs. Peptidomimetics offer an exciting class of therapeutics as they can be designed to target specific PPIs by mimicking key recognition motifs found at critical points in the interface of PPIs (e.g., hotspots). In contrast to peptides, peptidomimetics do not possess a natural peptide backbone structure but present essential functional groups in a required three-dimensional pattern complimentary to the protein-binding pocket. This design feature overcomes many limitations of peptide therapeutics including limited stability toward peptidases, poor transport across biologic membranes, and poor target specificity. Equally important is deciphering the structural requirements and amino acid residues critical to PPIs. This review provides an up-to-date perspective of the complexity of cellular signaling and strategies for targeting PPIs in disease states, particularly in cancer, using peptidomimetics, and highlights that the rational design of agents that target PPIs is not only feasible but is of the utmost clinical importance. Mol Cancer Res 12(7) 967–78. ©2014 AACR.
Publisher: Wiley
Date: 05-2006
DOI: 10.1002/PROS.20307
Abstract: The ability of CD8(+) T-cells to induce prostate inflammation was examined using a prostate ovalbumin expressing transgenic mouse (POET) and/or adoptive transfer of T-cell receptor (TCR) transgenic T-cells (OT-I) that specifically recognize ovalbumin. Localization of inflammatory cells to prostate tissue was examined following T-cell activation via endogenous prostatic antigen, recombinant type 5 adenovirus carrying the gene coding ovalbumin (Ad5-mOVA), or adoptive transfer of in vitro antigen stimulated OT-I cells. Ovalbumin specific OT-I cells were activated by autologous prostate antigen and trafficked to the prostate, but did not induce inflammation unless present in overwhelming numbers ( approximately 65% of CD8(+) T-cells). Activation of antigen specific CD8(+) T-cells in vitro (peptide pulsed antigen presenting cells) or in vivo (Ad5-mOVA) induced transitory prostate inflammation, without induction of prostate pathology, regardless of CD4(+) T-cell availability. Inflammation also was observed in OT-I x POET mice but again, pathological effects were not observed. T lymphocytes specific for a prostate antigen are capable of inducing inflammatory infiltration of prostatic tissue rapidly following activation, but do not produce pathological prostate injury.
Location: United States of America
No related grants have been discovered for Robert Matusik.