Steroid Hormone Receptors and Signal Transduction Processes

Klinge, Carolyn M.

doi:10.1007/978-3-319-44675-2_9

Cited by 13 publications

(14 citation statements)

References 379 publications

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“…Ligand binding in the specific ligand binding pocket induces a conformational change of the receptor, leading to the release of the corepressors, the recruitment of co-activators and the subsequent transactivation of genes (11). A proportion of unligated NRs, and more specifically, several steroid hormones, reside in the nucleus bound to DNA (12). GR and MR are exceptions since they reside in the cytoplasm in association with a variety of proteins in the absence of ligand.…”

Section: Introductionmentioning

confidence: 99%

A comprehensive structural and functional analysis of the ligand binding domain of the nuclear receptor superfamily reveals highly conserved signaling motifs and two distinct canonical forms through evolution

et al. 2020

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Nuclear receptors (NRs) are transcriptional factors that play an essential role in all aspects of human development, metabolism and physiology. A prime example of a NR is the glucocorticoid receptor (GR). Structure-wise, the GR is typical of the NR superfamily, while its signaling is a part of multiple physiological mechanisms. In this study, using the GR and the steroid hormone receptors as a basis, an analysis of the structure, function and evolution of the NR ligand binding domain was conducted, while a list of NR mutations was composed in order to examine the effects of the mutations on NR structure and function. The results proposed 7 conserved signaling motifs and identified the amino acid repeating pattern 'LxxLL' or 'LLxxL' in the ligand binding domains (LBDs) of the NRs. Phylogenetic analysis revealed 4 distinct monophyletic branches, and it proposed new evolutionary relations between the LBD of NRs. Furthermore, structural and functional comparisons through NR LBD structures and their corresponding ligands displayed two major canonical forms, one for the steroid hormone-like cluster and another one for the thyroid hormone-like cluster. Last but not least, a new sub-cluster of estrogen receptor α with a specific canonical form has been identified. Although this sub-cluster has 98% similarity in sequence level with all known ERα, shows more significant structural similarity with the ERβ members (RMSD <2Å) rather than the ERα. In particular, the Y537S mutation, which is very common in breast cancer, creates this new transform of ERα'. ERα' is functionally and structurally more similar to ERβ, while still retaining some of its ERα characteristics. This new information may be of high importance in order to understand the signaling mechanisms underlying NRs and cancer.

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Section: Introductionmentioning

confidence: 99%

A comprehensive structural and functional analysis of the ligand binding domain of the nuclear receptor superfamily reveals highly conserved signaling motifs and two distinct canonical forms through evolution

et al. 2020

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“…As per the present literatures, the members comprising the SHR family are ER, PR, AR, mineralocorticoid receptor (MR), and glucocorticoid receptor (GR) (8). Though this review centers around ER, PR, and AR, all the SHR members structurally comprise of five domains, as discussed below ( Figure 1).…”

Section: Biology Of Steroid Hormone Receptors (Shrs): Structure and Fmentioning

confidence: 97%

“…In absence of a steroid hormone ligand, SHR remains sequestered by a chaperone, heat shock protein 90 (Hsp90) (4,8). In the classical mode of SHR activation, after ligand docking, a ligandspecific conformational modification of the receptor happens, permitting its dissociation from restrictive Hsp90 complex, followed by auto-phosphorylation (4,8,13). These modifications trigger homo-or heterodimerization of SHR, followed by its nuclear translocation and subsequent binding to hormone response element (HRE) in a target gene.…”

Section: Classical Mode Of Shr Functionsmentioning

confidence: 99%

“…These modifications trigger homo-or heterodimerization of SHR, followed by its nuclear translocation and subsequent binding to hormone response element (HRE) in a target gene. This, in turn, initiates the SHR-driven transcriptional regulation of a target gene (4,8). The ligand-induced conformational modification of a SHR also facilitates its association/dissociation with coregulator complexes, during the course of transcription (4,8,12,14).…”

Section: Classical Mode Of Shr Functionsmentioning

confidence: 99%

“…The unanimous role of SHRs as transcription factors is widely worked upon in various research findings (4,8,53). Additionally, its non-genomic role is also established through a number of elegant works (20,21).…”

Section: Role Of Shrs In Cell Cycle Regulationmentioning

confidence: 99%

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Steroid Hormone Receptors: Links With Cell Cycle Machinery and Breast Cancer Progression

2021

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Progression of cells through cell cycle consists of a series of events orchestrated in a regulated fashion. Such processes are influenced by cell cycle regulated expression of various proteins where multiple families of transcription factors take integral parts. Among these, the steroid hormone receptors (SHRs) represent a connection between the external hormone milieu and genes that control cellular proliferation. Therefore, understanding the molecular connection between the transcriptional role of steroid hormone receptors and cell cycle deserves importance in dissecting cellular proliferation in normal as well as malignant conditions. Deregulation of cell cycle promotes malignancies of various origins, including breast cancer. Indeed, SHR members play crucial role in breast cancer progression as well as management. This review focuses on SHR-driven cell cycle regulation and moving forward, attempts to discuss the role of SHR-driven crosstalk between cell cycle anomalies and breast cancer.

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Mechanistic effects of arsenic trioxide on acute promyelocytic leukemia and other types of leukemias

Yousefnia

2021

Cell Biology International

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Acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia characterized with a translocation between promyelocytic leukemia gene (PML) on chromosome 15 and retinoic acid receptor alpha gene (RARα) on chromosome 17. Transcription of this fusion gene results in PML/RARα fusion protein blocking expression of critical genes involved in differentiation of myeloid cells through interaction with RAR element. PML/RARα fusion protein prevents normal function of PML and RARα as well as inhibiting apoptosis. Arsenic trioxide (ATO) is an important agent for the treatment of relapsed and newly diagnosed APL. ATO induces apoptosis, autophagy, and partial cellular differentiation as well as inhibiting cell growth and angiogenesis. Recognition of signaling pathways and molecular mechanisms induced by ATO can be effective for discovering novel treatment strategies to target leukemia cells. Also, it can be developed for the treatment of a variety of cancer cells. This review provides a perspective on anticancerous effects of ATO on APL and leukemia cells.

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Steroid Hormone Receptors and Signal Transduction Processes

Cited by 13 publications

References 379 publications

A comprehensive structural and functional analysis of the ligand binding domain of the nuclear receptor superfamily reveals highly conserved signaling motifs and two distinct canonical forms through evolution

A comprehensive structural and functional analysis of the ligand binding domain of the nuclear receptor superfamily reveals highly conserved signaling motifs and two distinct canonical forms through evolution

Steroid Hormone Receptors: Links With Cell Cycle Machinery and Breast Cancer Progression

Mechanistic effects of arsenic trioxide on acute promyelocytic leukemia and other types of leukemias

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