Protein Isoforms

Publication Title: 
Cellular and molecular life sciences: CMLS

Cell adhesion molecule 1 (CADM1), expressed by human lung mast cells (HLMCs), mediates their adhesion to airway smooth muscle (ASM), and contributes to ASM-dependent HLMC proliferation and survival. CADM1 is expressed in alternatively spliced isoforms, but those present in HLMCs and their function are not known. We cloned three functional and one cryptic non-functional isoform with alternative splicing between exons 7/11 and 1/2, respectively, from HLMCs and human MC lines (HMC-1 and LAD2).

Author(s): 
Moiseeva, Elena P.
Leyland, Mark L.
Bradding, Peter
Publication Title: 
Methods in Molecular Biology (Clifton, N.J.)

p53, a guardian of the genome, exerts its tumor suppression activity by regulating a large number of downstream targets involved in cell cycle arrest, DNA repair, apoptosis, and cellular senescence. Although p53-mediated apoptosis is able to kill cancer cells, a role for cellular senescence in p53-dependent tumor suppression is becoming clear. Mouse studies showed that activation of p53-induced premature senescence promotes tumor regression in vivo.

Author(s): 
Qian, Yingjuan
Chen, Xinbin
Publication Title: 
Aging Cell

A naturally occurring p53 isoform that lacks 39 residues at the N-terminus (denoted ?Np53), when expressed with wild-type p53 (WTp53), forms mixed ?Np53:WTp53 tetramers and causes accelerated aging in mice. Cellular alterations specific to ?Np53:WTp53 have been difficult to assess because ?Np53 and WTp53 coexpression results in tetramer heterogeneity, including formation of contaminating WTp53 tetramers. Based on the p53 tetramer structure, we expressed ?Np53 and WTp53 as a single transcript that maintained tetramer architecture, ensuring a 2:2 ?Np53:WTp53 stoichiometry.

Author(s): 
Lin, Shih-Chieh
Karoly, Edward D.
Taatjes, Dylan J.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Mutations in the clk-1 gene of the nematode Caenorhabditis elegans result in slowed development, sluggish adult behaviors, and an increased lifespan. CLK-1 is a mitochondrial polypeptide with sequence and functional conservation from human to yeast. Coq7p, the Saccharomyces cerevisiae homologue, is essential for ubiquinone (coenzyme Q or Q) synthesis and therefore respiration. However, based on assays of respiratory function, it has been reported that the primary defect in the C. elegans clk-1 mutants is not in Q biosynthesis.

Author(s): 
Jonassen, T.
Larsen, P. L.
Clarke, C. F.
Publication Title: 
Perspectives on Developmental Neurobiology

Cerebellar granule cells isolated from postnatal day 7 rat pups are ideal for studying epigenetic events associated with the regulation of neuronal gene expression. These cultures contain from 90 to 95% glutamatergic granule cells and express mRNAs encoding a variety of ionotropic and metabotropic glutamate receptors as well as virtually all of the GABAA-receptor subunit mRNAs to different extents. A unique feature of this culture system is that the neurons undergo time-dependent maturation changes in vitro that mimic many of the characteristics of these receptors occurring in vivo.

Author(s): 
Grayson, D. R.
Zhu, W.
Harris, B. T.
Vicini, S.
Zheng, T.
Publication Title: 
Archives of General Psychiatry

CONTEXT: Although most of the effort to understand the neurobiology of depressive states and suicide has focused on neuronal processes, recent studies suggest that astroglial dysfunction may play an important role. A truncated variant of the tropomyosin-related kinase B (TrkB.T1) is expressed in astrocytes, and brain-derived neurotrophic factor-TrkB signaling has been linked to mood disorders. OBJECTIVE: To test the hypothesis that TrkB.T1 expression is downregulated in suicide completers and that this downregulation is mediated by an epigenetic process.

Author(s): 
Ernst, Carl
Deleva, Vesselina
Deng, Xiaoming
Sequeira, Adolfo
Pomarenski, Amanda
Klempan, Tim
Ernst, Neil
Quirion, Rémi
Gratton, Alain
Szyf, Moshe
Turecki, Gustavo
Publication Title: 
Oxidative Medicine and Cellular Longevity

Epigenetic modifications like DNA methylation and histone acetylation play an important role in a wide range of brain disorders. Histone deacetylases (HDACs) regulate the homeostasis of histone acetylation. Histone deacetylase inhibitors, which initially were used as anticancer drugs, are recently suggested to act as neuroprotectors by enhancing synaptic plasticity and learning and memory in a wide range of neurodegenerative and psychiatric disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD).

Author(s): 
Xu, Ke
Dai, Xue-Ling
Huang, Han-Chang
Jiang, Zhao-Feng
Publication Title: 
Schizophrenia Research

INTRODUCTION: To improve the understanding of psychotic abnormalities and their non-Mendelian inheritance patterns, the epigenetic regulation of the psychotic disorder-associated GABRB2, gene for the type A ?-aminobutyric acid receptor ?(2)-subunit, was investigated. METHODS: Expression of GABRB2, and the epigenetic regulatory enzymes histone deacetylases (HDACs) and DNA methyltransferases (DNMTs) in mouse and postmortem human brains was analyzed using real-time PCR.

Author(s): 
Zhao, Cunyou
Wang, Feng
Pun, Frank W.
Mei, Lingling
Ren, Lihuan
Yu, Zhiliang
Ng, Siu-Kin
Chen, Jianhuan
Tsang, Shui-Ying
Xue, Hong
Publication Title: 
Molecular Psychiatry

Adenosine-to-inosine (A-to-I) RNA editing is a neurodevelopmentally regulated epigenetic modification shown to modulate complex behavior in animals. Little is known about human A-to-I editing, but it is thought to constitute one of many molecular mechanisms connecting environmental stimuli and behavioral outputs. Thus, comprehensive exploration of A-to-I RNA editing in human brains may shed light on gene-environment interactions underlying complex behavior in health and disease.

Author(s): 
Eran, A.
Li, J. B.
Vatalaro, K.
McCarthy, J.
Rahimov, F.
Collins, C.
Markianos, K.
Margulies, D. M.
Brown, E. N.
Calvo, S. E.
Kohane, I. S.
Kunkel, L. M.
Publication Title: 
Future Medicinal Chemistry

Increasing evidence supports a role for epigenetic involvement in some of the neurobiological alterations observed in neurodegenerative and psychiatric disorders including schizophrenia. In particular, there is mounting evidence implicating dysfunction in acetylation status, a chromatin modification mediated in part by HDACs, as a possible contributing factor to certain facets of this debilitating disease.

Author(s): 
WeÔwer, Michel
Lewis, Michael C.
Wagner, Florence F.
Holson, Edward B.

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