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Androgen signaling uses a writer and a reader of ADP-ribosylation to regulate protein complex assembly
Androgen receptor (AR) signaling is regulated by multiple post-translational modifications. Here, the authors identify the writer and reader enzymes for AR ADP-ribosylation and show how they modulate AR signaling output in prostate cancer cells.
- Chun-Song Yang
- , Kasey Jividen
- & Bryce M. Paschal
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Article
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Genome-wide binding potential and regulatory activity of the glucocorticoid receptor’s monomeric and dimeric forms
Glucocorticoid receptors (GR) are thought to bind DNA as dimers or monomers, to regulate different transcription pathways. Here, the authors perform genome-wide studies on GRs with mutations that impair dimerization and provide evidence that monomeric GRs do not play a significant physiologic role.
- Thomas A. Johnson
- , Ville Paakinaho
- & Diego M. Presman
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Article
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Crystal structure of steroid reductase SRD5A reveals conserved steroid reduction mechanism
Steroid 5α-reductase 2 (SRD5A2), a testosterone metabolism enzyme, is implicated in human disease. Structural and biochemical analyses of PbSRD5A, a bacterial homolog, reveal SRD5A2 substrate binding pocket and provide framework for the design of new drugs targeting this enzyme.
- Yufei Han
- , Qian Zhuang
- & Ruobing Ren
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Article
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The circadian cryptochrome, CRY1, is a pro-tumorigenic factor that rhythmically modulates DNA repair
Cryptochrome 1 (CRY1) is a transcriptional coregulator associated with the circadian clock. Here the authors reveal that CRY1 is hormone-regulated, stabilized by genomic insult, and promotes DNA repair and cell survival through temporal transcriptional regulation.
- Ayesha A. Shafi
- , Chris M. McNair
- & Karen E. Knudsen
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Structure of human steroid 5α-reductase 2 with the anti-androgen drug finasteride
Human steroid 5α-reductase 2 (SRD5A2) is an integral membrane enzyme and catalyzes 5α-reduction of testosterone to dihydrotestosterone. Structural analysis accompanied by computational and mutagenesis studies reveal the mechanisms of catalysis and inhibition by clinically relevant drugs targeting SRD5A2.
- Qingpin Xiao
- , Lei Wang
- & Cheng Zhang
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Glycogen branching enzyme controls cellular iron homeostasis via Iron Regulatory Protein 1 and mitoNEET
Higher organisms regulate cellular iron concentrations through Iron Regulatory Proteins (IRPs), which regulate specific messenger RNAs. Here Huynh et al. show that IRP1 requires a Glycogen Branching Enzyme for proper function, and that IRP1 has additional regulatory roles in cell nuclei.
- Nhan Huynh
- , Qiuxiang Ou
- & Kirst King-Jones
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E47 modulates hepatic glucocorticoid action
Glucocorticoids (GCs) are widely used anti-inflammatory drugs; however, long-term treatment causes metabolic side effects. Here, the authors show that E47 is a modulator of glucocorticoid receptor activity for a subset of target genes in mouse liver, and that loss of E47 protects mice from hyperglycemia and hepatic steatosis in response to GCs.
- M. Charlotte Hemmer
- , Michael Wierer
- & N. Henriette Uhlenhaut
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Bone corticalization requires local SOCS3 activity and is promoted by androgen action via interleukin-6
The strength of long bones is determined by coalescence of trabeculae during corticalization. Here the authors show that this process is regulated by SOCS3 via a mechanism dependent on IL-6 and expression of sex hormones.
- Dae-Chul Cho
- , Holly J. Brennan
- & Natalie A. Sims
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Article
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Molecular evidence of functional progesterone withdrawal in human myometrium
How human labour is initiated in the presence of high circulating progesterone is still unclear. Here, the authors show that during a reduction in myometrial nuclear progesterone levels, there is an increased transcription of the key labour gene, Cx43, mediated by unliganded progesterone receptor A.
- Lubna Nadeem
- , Oksana Shynlova
- & Stephen Lye
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Steroid binding to Autotaxin links bile salts and lysophosphatidic acid signalling
Autotaxin generates the bioactive lipid lysophosphatidic acid to regulate diverse biological processes. Here, the authors identify a role for bile salts as direct allosteric inhibitors of autotaxin activity, suggesting that steroids may function as regulators of lysophosphatidic acid signalling.
- Willem-Jan Keune
- , Jens Hausmann
- & Anastassis Perrakis
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Sex bias in CNS autoimmune disease mediated by androgen control of autoimmune regulator
Males are less susceptible to autoimmune diseases due to immunomodulatory effects of androgen. Here the authors show that androgen receptor upregulates Aire and Aire-dependent transcription in the thymic epithelium, and that Aire is required for androgen-mediated suppression of experimental autoimmune encephalitis.
- Meng-Lei Zhu
- , Pearl Bakhru
- & Maureen A. Su
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Steroid hormone signalling links reproduction to lifespan in dietary-restricted Caenorhabditis elegans
Dietary restriction increases the lifespan of many species, but often at the cost of reduced fertility. Here, Thondamal et al. show that the dietary restriction-mediated increase in lifespan in Caenorhabditis elegansdepends on the production of a steroid hormone and its inhibition of germline plasticity.
- Manjunatha Thondamal
- , Michael Witting
- & Hugo Aguilaniu
Cryo-EM reveals the architecture of the PELP1-WDR18 molecular scaffold