The enhancement of nuclear receptor transcriptional activation by a mouse actin-binding protein, alpha actinin 2

Huang, Shih‐Ming; Huang, Chunjian; Wang, W M; Kang, Jiuhong; Hsu, Wen Lin

doi:10.1677/jme.0.0320481

Cited by 37 publications

(37 citation statements)

References 54 publications

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“…For example, paxillin can recruit rho guanine nucleotide exchange factors to cell–extracellular matrix contact sites which leads to downstream cell migration activity [32]. The actinin α2 and transgelin proteins have been reported to regulate AR-mediated transcription [33, 34], whereas TSC22 domain family member 1 has been shown to be regulated by the androgen receptor [35]. The recognition of these particular antigens might have been directly influenced by changes in expression levels following androgen deprivation.…”

Section: Discussionmentioning

confidence: 99%

Prostate cancer patients on androgen deprivation therapy develop persistent changes in adaptive immune responses

Morse¹,

McNeel²

2010

Human Immunology

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Prostate cancer is a significant cause of morbidity and mortality among men worldwide. The cornerstone treatment for metastatic prostate cancer is androgen deprivation, which has known effects on prostate tissue apoptosis and thymic regrowth. These findings, plus interest in developing immune-based treatments for prostate cancer, lead us to question whether androgen deprivation causes changes in the adaptive immune responses of prostate cancer patients, and if the timing of changes has implications for the sequencing of immunotherapies in combination with androgen deprivation. Peripheral blood mononuclear cells (PBMC) were obtained from patients prior to beginning androgen deprivation therapy (ADT) and at several time points thereafter. These cells were analyzed for the frequency of specific lymphocyte populations, and their response to stimulation. The development of prostate antigen-specific immune responses was assessed using SEREX. Patients developed expansion of the naïve T cell compartment persisting over the course of androgen deprivation, together with an increase in effector cell response to stimulation, and the generation of prostate tissue-associated IgG antibody responses, implying a potential benefit to the use of ADT in combination with prostate cancer-directed immunotherapies. The optimal timing and sequence of androgen deprivation with immune-based therapies awaits future experimental evaluation.

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Section: Discussionmentioning

confidence: 99%

Prostate cancer patients on androgen deprivation therapy develop persistent changes in adaptive immune responses

Morse¹,

McNeel²

2010

Human Immunology

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“…This naturally occurring filamin fragment represses AR transactivation and disrupts AR interdomain interactions as well as hampers SRC-2-activated AR function. Another cytoskeletal protein, ␣-actinin-2, enhances the transactivation activity of SRC-2 and serves as a primary coactivator for the AR, acting in synergy with SRC-2 to increase AR transactivation function (166). ␣-Actinin-4 also binds to the AR and exhibits coregulating properties (167).…”

Section: Chaperones and Cochaperonesmentioning

confidence: 99%

Androgen Receptor (AR) Coregulators: A Diversity of Functions Converging on and Regulating the AR Transcriptional Complex

2007

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Androgens, acting through the androgen receptor (AR), are responsible for the development of the male phenotype during embryogenesis, the achievement of sexual maturation at puberty, and the maintenance of male reproductive function and behavior in adulthood. In addition, androgens affect a wide variety of nonreproductive tissues. Moreover, aberrant androgen action plays a critical role in multiple pathologies, including prostate cancer and androgen insensitivity syndromes. The formation of a productive AR transcriptional complex requires the functional and structural interaction of the AR with its coregulators. In the last decade, an overwhelming and ever increasing number of proteins have been proposed to possess AR coactivating or corepressing characteristics. Intriguingly, a vast diversity of functions has been ascribed to these proteins, indicating that a multitude of cellular functions and signals converge on the AR to regulate its function. The current review aims to provide an overview of the AR coregulator proteins identified to date and to propose a classification of these AR coregulator proteins according to the function(s) ascribed to them. Taken together, this approach will increase our understanding of the cellular pathways that converge on the AR to ensure an appropriate transcriptional response to androgens.

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“…The subunit of the TRAP/DRIP complex that is responsible for interaction with the LBD of activated receptors was identified as TRAP220/DRIP205 and harbors a functional LxxLL NR box motif (Yuan et al, 1998;Rachez et al, 1999;692 Yang and Freedman, 1999). New coregulators are continually being discovered, and these include factors that were not expected to serve such functions, e.g., the RNA transcript for the steroid receptor-RNA activator-1 coactivator, the NAD/NADH sensor C-terminal binding protein of E1A, and several actin-binding proteins (Lanz et al, 1999;Kumar et al, 2002;Ting et al, 2002;Loy et al, 2003;Nishimura et al, 2003;Yoon et al, 2003;Huang et al, 2004;Kumar et al, 2004;Lee et al, 2004). An exhaustive list of known coregulators can be found in several reviews (Cosma, 2002;Hermanson et al, 2002;Kraus and Wong, 2002;Privalsky, 2004).…”

Section: Transcriptional Activationmentioning

confidence: 99%

Overview of Nomenclature of Nuclear Receptors

Germain¹,

Staels²,

Dacquet³

et al. 2006

Pharmacol Rev

559

443

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Abstract--Nuclear receptor pharmacology has, to a certain extent, led the way, compared with other receptor systems, in the appreciation that ligands may exert very diverse pharmacology, based on their individual chemical structure and the allosteric changes induced in the receptor/accessory protein complex. This can lead to very selective pharmacological effects, which may not necessarily be predicted from the experience with other agonists/partial agonists/antagonists. If this is the case, then drug discovery may be back to drug-specific pharmacology (where each drug may have an original profile), rather than specificdrug pharmacology (where agents specific for a receptor have a distinct profile). As functional selectivity is indeed a crucial mechanism to be considered when going through the drug discovery development process, then initial screens using reconstituted systems may not show the appropriate pharmacology, simply because the required stoichiometry of corepressors and coactivators may not be present to select the best compounds; therefore, multiple effector systems are necessary to screen for differential activation, and, even then, screening with in vivo pathophysiological models may ultimately be required for the selection process-a massive but necessary task for pharmacologists. Thus, the characterization of nuclear receptors and their associated proteins and the ligands that interact with them will remain a challenge to pharmacologists.

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The enhancement of nuclear receptor transcriptional activation by a mouse actin-binding protein, alpha actinin 2

Cited by 37 publications

References 54 publications

Prostate cancer patients on androgen deprivation therapy develop persistent changes in adaptive immune responses

Prostate cancer patients on androgen deprivation therapy develop persistent changes in adaptive immune responses

Androgen Receptor (AR) Coregulators: A Diversity of Functions Converging on and Regulating the AR Transcriptional Complex

Overview of Nomenclature of Nuclear Receptors

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