Protein Precursors

Publication Title: 
Genes & Development

Alterations in the architecture and dynamics of the nuclear lamina have a causal role in normal and accelerated aging through both cell-autonomous and systemic mechanisms. However, the precise nature of the molecular cues involved in this process remains incompletely defined. Here we report that the accumulation of prelamin A isoforms at the nuclear lamina triggers an ATM- and NEMO-dependent signaling pathway that leads to NF-?B activation and secretion of high levels of proinflammatory cytokines in two different mouse models of accelerated aging (Zmpste24(-/-) and Lmna(G609G/G609G) mice).

Author(s): 
Osorio, Fernando G.
B·rcena, Clea
Soria-Valles, Clara
Ramsay, Andrew J.
de Carlos, FÈlix
Cobo, Juan
Fueyo, Antonio
Freije, JosÈ M. P.
LÛpez-OtÌn, Carlos
Publication Title: 
Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire

My desire as a young endocrinologist to improve my clinical skills through a better knowledge of hormone chemistry led me to serendipitous discoveries and unexpected horizons. The first discovery, published in 1967, revealed that peptide hormones are derived from endoproteolytic cleavages of larger precursor polypeptides. It was the foundation of the prohormone theory.

Author(s): 
ChrÈtien, Michel
Publication Title: 
Cell Metabolism

Abnormal splicing of LMNA gene or aberrant processing of prelamin A results in progeroid syndrome. Here we show that lamin A interacts with and activates SIRT1. SIRT1 exhibits reduced association with nuclear matrix (NM) and decreased deacetylase activity in the presence of progerin or prelamin A,†leading to rapid depletion of adult stem cells (ASCs) in Zmpste24(-/-) mice. Resveratrol enhances the binding between SIRT1 and A-type lamins to increases its deacetylase activity.

Author(s): 
Liu, Baohua
Ghosh, Shrestha
Yang, Xi
Zheng, Huiling
Liu, Xinguang
Wang, Zimei
Jin, Guoxiang
Zheng, Bojian
Kennedy, Brian K.
Suh, Yousin
Kaeberlein, Matt
Tryggvason, Karl
Zhou, Zhongjun
Publication Title: 
Nature Communications

A de novo G608G mutation in LMNA gene leads to Hutchinson-Gilford progeria syndrome. Mice lacking the prelamin A-processing metalloprotease, Zmpste24, recapitulate many of the progeroid features of Hutchinson-Gilford progeria syndrome. Here we show that A-type lamins interact with SUV39H1, and prelamin A/progerin exhibits enhanced binding capacity to SUV39H1, protecting it from proteasomal degradation and, consequently, increasing H3K9me3 levels. Depletion of Suv39h1 reduces H3K9me3 levels, restores DNA repair capacity and delays senescence in progeroid cells.

Author(s): 
Liu, Baohua
Wang, Zimei
Zhang, Le
Ghosh, Shrestha
Zheng, Huiling
Zhou, Zhongjun
Publication Title: 
Epigenetics

Early-life stress induces persistent memory traces on our genes and programs the life-long risk for depression. Epigenetic marking of the arginine vasopressin (AVP) gene by early-life stress in mice underpins sustained expression and increased hypothalamic-pituitary-adrenal axis activity, triggering endocrine and behavioral alterations that are frequent features in depression. This epigenetic memory evolves in two steps coordinated by the epigenetic reader and writer MeCP2.

Author(s): 
Murgatroyd, Chris
Wu, Yonghe
Bockm¸hl, Yvonne
Spengler, Dietmar
Publication Title: 
Pharmacogenetics and Genomics

OBJECTIVE: Dynorphins, the endogenous ligands for the ? opioid receptor, are implicated in neuropsychiatric disorders through modulation of basal and stimuli-induced dopaminergic, glutamatergic, and serotonergic tones. Expression of the prodynorphin gene (PDYN) is critical for rewarding properties of drugs of abuse and stress-induced responses. Epigenetic factors, such as DNA methylation, play an important role in modulation of gene expression.

Author(s): 
Yuferov, Vadim
Nielsen, David A.
Levran, Orna
Randesi, Matthew
Hamon, Sara
Ho, Ann
Morgello, Susan
Kreek, Mary Jeanne
Publication Title: 
Biological Psychiatry

BACKGROUND: Prenatal cannabis exposure has been linked to addiction vulnerability, but the neurobiology underlying this risk is unknown. METHODS: Striatal dopamine and opioid-related genes were studied in human fetal subjects exposed to cannabis (as well as cigarettes and alcohol). Cannabis-related gene disturbances observed in the human fetus were subsequently characterized with an animal model of prenatal ?-9-tetrahydrocannabinol (THC) (.15 mg/kg) exposure.

Author(s): 
DiNieri, Jennifer A.
Wang, Xinyu
Szutorisz, Henrietta
Spano, Sabrina M.
Kaur, Jasbir
Casaccia, Patrizia
Dow-Edwards, Diana
Hurd, Yasmin L.
Publication Title: 
Cellular and molecular life sciences: CMLS

The dynorphin/?-opioid receptor system has been implicated in the pathogenesis and pathophysiology of several psychiatric disorders. In the present review, we present evidence indicating a key role for this system in modulating neurotransmission in brain circuits that subserve mood, motivation, and cognitive function.

Author(s): 
Tejeda, H. A.
Shippenberg, T. S.
Henriksson, R.
Publication Title: 
Biological Psychiatry

BACKGROUND: Marijuana use by teenagers often predates the use of harder drugs, but the neurobiological underpinnings of such vulnerability are unknown. Animal studies suggest enhanced heroin self-administration (SA) and dysregulation of the endogenous opioid system in the nucleus accumbens shell (NAcsh) of adults following adolescent ?(9)-tetrahydrocannabinol (THC) exposure. However, a causal link between proenkephalin (Penk) expression and vulnerability to heroin has yet to be established.

Author(s): 
Tomasiewicz, Hilarie C.
Jacobs, Michelle M.
Wilkinson, Matthew B.
Wilson, Steven P.
Nestler, Eric J.
Hurd, Yasmin L.
Publication Title: 
Trends in Neurosciences

Addictions to cocaine or heroin/prescription opioids [short-acting ?-opioid receptor (MOPr) agonists] involve relapsing cycles, with experimentation/escalating use, withdrawal/abstinence, and relapse/re-escalation. ?-Opioid receptors (KOPr; encoded by OPRK1), and their endogenous agonists, the dynorphins (encoded by PDYN), have counter-modulatory effects on reward caused by cocaine or MOPr agonist exposure, and exhibit plasticity in addictive-like states. KOPr/dynorphin activation is implicated in depression/anxiety, often comorbid with addictions.

Author(s): 
Butelman, Eduardo R.
Yuferov, Vadim
Kreek, Mary Jeanne

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