Intracellular Peptides in Cell Biology and Pharmacology

Biomolecules - Tập 9 Số 4 - Trang 150
Christiane B. de Araujo1, Andrea S. Heimann2, Ricardo A. Remer3, Lilian C. Russo4, Alison Colquhoun5, Fábio Luís Forti4, Emer S. Ferro6
1Special Laboratory of Cell Cycle, Center of Toxins, Immune Response and Cell Signaling—CeTICS, Butantan Institute, São Paulo SP 05503-900, Brazil
2Proteimax Biotecnologia LTDA, São Paulo SP 05581-001, Brazil
3Remer Consultores Ltda., São Paulo SP 01411-001, Brazil
4Department of Biochemistry, Chemistry Institute, University of São Paulo 1111, São Paulo 05508-000, Brazil
5Department of Cell and Developmental Biology, University of São Paulo (USP), São Paulo 05508-000, Brazil
6Department of Pharmacology, Biomedical Sciences Institute, University of São Paulo (USP), São Paulo 05508-000, Brazil

Tóm tắt

Intracellular peptides are produced by proteasomes following degradation of nuclear, cytosolic, and mitochondrial proteins, and can be further processed by additional peptidases generating a larger pool of peptides within cells. Thousands of intracellular peptides have been sequenced in plants, yeast, zebrafish, rodents, and in human cells and tissues. Relative levels of intracellular peptides undergo changes in human diseases and also when cells are stimulated, corroborating their biological function. However, only a few intracellular peptides have been pharmacologically characterized and their biological significance and mechanism of action remains elusive. Here, some historical and general aspects on intracellular peptides’ biology and pharmacology are presented. Hemopressin and Pep19 are examples of intracellular peptides pharmacologically characterized as inverse agonists to cannabinoid type 1 G-protein coupled receptors (CB1R), and hemopressin fragment NFKF is shown herein to attenuate the symptoms of pilocarpine-induced epileptic seizures. Intracellular peptides EL28 (derived from proteasome 26S protease regulatory subunit 4; Rpt2), PepH (derived from Histone H2B type 1-H), and Pep5 (derived from G1/S-specific cyclin D2) are examples of peptides that function intracellularly. Intracellular peptides are suggested as biological functional molecules, and are also promising prototypes for new drug development.

Từ khóa


Tài liệu tham khảo

Fricker, 2005, Neuropeptide-processing enzymes: Applications for drug discovery, AAPS J., 7, E449, 10.1208/aapsj070244

Glickman, 2002, The ubiquitin-proteasome proteolytic pathway: Destruction for the sake of construction, Physiol. Rev., 82, 373, 10.1152/physrev.00027.2001

Dolan, 2011, Translating DRiPs: Progress in understanding viral and cellular sources of MHC class I peptide ligands, Cell. Mol. Life Sci., 68, 1481, 10.1007/s00018-011-0656-z

Lee, 2015, The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance, Cell Metab., 21, 443, 10.1016/j.cmet.2015.02.009

Rist, 2013, HLA peptide length preferences control CD8+ T cell responses, J. Immunol., 191, 561, 10.4049/jimmunol.1300292

Burrows, 2008, Preferential binding of unusually long peptides to MHC class I and its influence on the selection of target peptides for T cell recognition, Mol. Immunol., 45, 1818, 10.1016/j.molimm.2007.09.026

Kloverpris, 2013, HLA-specific intracellular epitope processing shapes an immunodominance pattern for HLA-B*57 that is distinct from HLA-B*58:01, J. Virol., 87, 10889, 10.1128/JVI.01122-13

Caron, 2015, Analysis of Major Histocompatibility Complex (MHC) Immunopeptidomes Using Mass Spectrometry, Mol. Cell. Proteom., 14, 3105, 10.1074/mcp.O115.052431

Connell, 1957, Intracellular peptides of Pseudomonas hydrophila, Biochim. Biophys. Acta, 24, 226, 10.1016/0006-3002(57)90184-1

McManus, 1958, Synthesis of intracellular peptides in Torula utilis, J. Biol. Chem., 231, 777, 10.1016/S0021-9258(18)70441-9

Guidotti, 1983, Isolation, characterization, and purification to homogeneity of an endogenous polypeptide with agonistic action on benzodiazepine receptors, Proc. Natl. Acad. Sci. USA, 80, 3531, 10.1073/pnas.80.11.3531

Alho, 1985, Diazepam-binding inhibitor: A neuropeptide located in selected neuronal populations of rat brain, Science, 229, 179, 10.1126/science.3892688

Huyer, 2006, Saccharomyces cerevisiae a-factor mutants reveal residues critical for processing, activity, and export, Eukaryot. Cell, 5, 1560, 10.1128/EC.00161-06

Rioli, 2003, Novel natural peptide substrates for endopeptidase 24.15, neurolysin, and angiotensin-converting enzyme, J. Biol. Chem., 278, 8547, 10.1074/jbc.M212030200

Rioli, 2018, Substrate Capture Assay Using Inactive Oligopeptidases to Identify Novel Peptides, Methods Mol. Biol., 1719, 97, 10.1007/978-1-4939-7537-2_6

Dale, 2005, Hemopressin: A novel bioactive peptide derived from the alpha1-chain of hemoglobin, Mem Inst. Oswaldo Cruz, 100, 105, 10.1590/S0074-02762005000900017

Heimann, 2005, ACE gene titration in mice uncovers a new mechanism for ACE on the control of body weight, Physiol. Genom., 20, 173, 10.1152/physiolgenomics.00145.2004

Machado, 2006, Substrate phosphorylation affects degradation and interaction to endopeptidase 24.15, neurolysin, and angiotensin-converting enzyme, Biochem. Biophys. Res. Commun., 339, 520, 10.1016/j.bbrc.2005.11.041

Ferro, 2004, Intracellullar peptides as putative natural regulators of protein interactions, J. Neurochem., 91, 769, 10.1111/j.1471-4159.2004.02757.x

Fesenko, I.A., Arapidi, G.P., Skripnikov, A.Y., Alexeev, D.G., Kostryukova, E.S., Manolov, A.I., Altukhov, I.A., Khazigaleeva, R.A., Seredina, A.V., and Kovalchuk, S.I. (2015). Specific pools of endogenous peptides are present in gametophore, protonema, and protoplast cells of the moss Physcomitrella patens. BMC Plant. Biol., 15.

Fesenko, 2018, Analysis of Endogenous Peptide Pools of Physcomitrella patens Moss, Methods Mol. Biol., 1719, 395, 10.1007/978-1-4939-7537-2_27

Dasgupta, S., Yang, C., Castro, L.M., Tashima, A.K., Ferro, E.S., Moir, R.D., Willis, I.M., and Fricker, L.D. (2016). Analysis of the Yeast Peptidome and Comparison with the Human Peptidome. PLoS ONE, 11.

Teixeira, C.M.M., Correa, C.N., Iwai, L.K., Ferro, E.S., and Castro, L.M. (2019). Characterization of intracellular peptides from zebrafish Danio rerio brain”. Zebrafish.

Fricker, 2010, Analysis of mouse brain peptides using mass spectrometry-based peptidomics: Implications for novel functions ranging from non-classical neuropeptides to microproteins, Mol. Biosyst., 6, 1355, 10.1039/c003317k

Gelman, 2010, Hemopressins and other hemoglobin-derived peptides in mouse brain: Comparison between brain, blood, and heart peptidome and regulation in Cpefat/fat mice, J. Neurochem., 113, 871, 10.1111/j.1471-4159.2010.06653.x

Berezniuk, 2010, CCP1/Nna1 functions in protein turnover in mouse brain: Implications for cell death in Purkinje cell degeneration mice, FASEB J., 24, 1813, 10.1096/fj.09-147942

Berti, 2009, Analysis of intracellular substrates and products of thimet oligopeptidase in human embryonic kidney 293 cells, J. Biol. Chem., 284, 14105, 10.1074/jbc.M807916200

Gelman, 2011, Peptidomic analysis of human cell lines, J. Proteom. Res., 10, 1583, 10.1021/pr100952f

Dasgupta, S., Castro, L.M., Dulman, R., Yang, C., Schmidt, M., Ferro, E.S., and Fricker, L.D. (2014). Proteasome inhibitors alter levels of intracellular peptides in HEK293T and SH-SY5Y cells. PLoS ONE, 9.

Ferro, 2017, Peptidomic analysis of the anterior temporal lobe and corpus callosum from schizophrenia patients, J. Proteom., 151, 97, 10.1016/j.jprot.2016.05.025

Li, 2018, Identification of intracellular peptides associated with thermogenesis in human brown adipocytes, J. Cell. Physiol., 234, 7104, 10.1002/jcp.27465

Murata, 2018, The immunoproteasome and thymoproteasome: Functions, evolution and human disease, Nat. Immunol., 19, 923, 10.1038/s41590-018-0186-z

Heimann, 2007, Hemopressin is an inverse agonist of CB1 cannabinoid receptors, Proc. Natl. Acad. Sci. USA, 104, 20588, 10.1073/pnas.0706980105

Dodd, 2010, The peptide hemopressin acts through CB1 cannabinoid receptors to reduce food intake in rats and mice, J. Neurosci., 30, 7369, 10.1523/JNEUROSCI.5455-09.2010

Gomes, 2009, Novel endogenous peptide agonists of cannabinoid receptors, FASEB J., 23, 3020, 10.1096/fj.09-132142

Gomes, 2010, Hemoglobin-derived peptides as novel type of bioactive signaling molecules, AAPS J., 12, 658, 10.1208/s12248-010-9217-x

Bauer, 2012, Identification and quantification of a new family of peptide endocannabinoids (Pepcans) showing negative allosteric modulation at CB1 receptors, J. Biol. Chem., 287, 36944, 10.1074/jbc.M112.382481

Hofer, 2015, Localization and production of peptide endocannabinoids in the rodent CNS and adrenal medulla, Neuropharmacology, 98, 78, 10.1016/j.neuropharm.2015.03.021

Xapelli, 2014, Modulation of subventricular zone oligodendrogenesis: A role for hemopressin?, Front. Cell. Neurosci., 8, 59, 10.3389/fncel.2014.00059

Khilnani, 2011, Inverse agonism and its therapeutic significance, Indian J. Pharmacol., 43, 492, 10.4103/0253-7613.84947

Bomar, 2012, Hemopressin forms self-assembled fibrillar nanostructures under physiologically relevant conditions, Biomacromolecules, 13, 579, 10.1021/bm201836f

Dale, 2005, Antinociceptive action of hemopressin in experimental hyperalgesia, Peptides, 26, 431, 10.1016/j.peptides.2004.10.026

Blais, 2005, Hypotensive effects of hemopressin and bradykinin in rabbits, rats and mice. A comparative study, Peptides, 26, 1317, 10.1016/j.peptides.2005.03.026

Lippton, 2006, Hemopressin, a hemoglobin fragment, dilates the rat systemic vascular bed through release of nitric oxide, Peptides, 27, 2284, 10.1016/j.peptides.2006.04.010

Gelman, 2010, Hemopressin and other bioactive peptides from cytosolic proteins: Are these non-classical neuropeptides?, AAPS J., 12, 279, 10.1208/s12248-010-9186-0

Scrima, 2010, Binding of the hemopressin peptide to the cannabinoid CB1 receptor: Structural insights, Biochemistry, 49, 10449, 10.1021/bi1011833

Horvath, 2011, Antinociception by endogenous ligands at peripheral level, Ideggyogy Sz, 64, 193

Hama, 2011, Activation of spinal and supraspinal cannabinoid-1 receptors leads to antinociception in a rat model of neuropathic spinal cord injury pain, Brain Res., 1412, 44, 10.1016/j.brainres.2011.07.031

Hama, 2011, Centrally mediated antinociceptive effects of cannabinoid receptor ligands in rat models of nociception, Pharmacol. Biochem. Behav., 100, 340, 10.1016/j.pbb.2011.09.004

Petrovszki, 2012, The effects of peptide and lipid endocannabinoids on arthritic pain at the spinal level, Anest. Anal.g, 114, 1346, 10.1213/ANE.0b013e31824c4eeb

Bomar, 2013, Modulation of the cannabinoid receptors by hemopressin peptides, Life Sci., 92, 520, 10.1016/j.lfs.2012.07.028

Zhou, 2012, Effects of endokinin A/B and endokinin C/D on the antinociception properties of hemopressin in mice, Peptides, 38, 70, 10.1016/j.peptides.2012.08.006

Reddy, 2012, Synthesis of hemopressin peptides by classical solution phase fragment condensation, Int. J. Pept., 2012, 186034, 10.1155/2012/186034

Gelman, 2013, Analysis of peptides secreted from cultured mouse brain tissue, Biochim. Biophys. Acta, 1834, 2408, 10.1016/j.bbapap.2013.01.043

Dodd, 2013, Central functional response to the novel peptide cannabinoid, hemopressin, Neuropharmacology, 71, 27, 10.1016/j.neuropharm.2013.03.007

Tanaka, 2014, Brain RVD-haemopressin, a haemoglobin-derived peptide, inhibits bombesin-induced central activation of adrenomedullary outflow in the rat, Br. J. Pharmacol., 171, 202, 10.1111/bph.12471

Rashid, 2014, Functional up-regulation of endopeptidase neurolysin during post-acute and early recovery phases of experimental stroke in mouse brain, J. Neurochem., 129, 179, 10.1111/jnc.12513

Han, 2014, Antinociceptive effects of central administration of the endogenous cannabinoid receptor type 1 agonist VDPVNFKLLSH-OH [(m)VD-hemopressin(alpha)], an N-terminally extended hemopressin peptide, J. Pharmacol. Exp. Ther., 348, 316, 10.1124/jpet.113.209866

Li, 2014, The hypotensive effect of intrathecally injected (m)VD-hemopressin(alpha) in urethane-anesthetized rats, Peptides, 56, 45, 10.1016/j.peptides.2014.03.012

Toniolo, 2014, Hemopressin, an inverse agonist of cannabinoid receptors, inhibits neuropathic pain in rats, Peptides, 56, 125, 10.1016/j.peptides.2014.03.016

Pan, 2014, Analgesic tolerance and cross-tolerance to the cannabinoid receptors ligands hemopressin, VD-hemopressin(alpha) and WIN55,212-2 at the supraspinal level in mice, Neurosci. Lett., 578, 187, 10.1016/j.neulet.2014.06.058

Mahmoud, 2014, Role of cannabinoid receptors in hepatic fibrosis and apoptosis associated with bile duct ligation in rats, Eur. J. Pharmacol., 742, 118, 10.1016/j.ejphar.2014.08.021

Fogaca, 2015, Anxiogenic-like effects induced by hemopressin in rats, Pharmacol. Biochem. Behav., 129, 7, 10.1016/j.pbb.2014.11.013

Song, 2015, Site-specific Substitutions Eliminate Aggregation Properties of Hemopressin, Chem. Biol. Drug Des., 86, 1433, 10.1111/cbdd.12610

Straiker, 2015, Aiming for allosterism: Evaluation of allosteric modulators of CB1 in a neuronal model, Pharmacol. Res., 99, 370, 10.1016/j.phrs.2015.07.017

Ma, 2015, Mitochondrial CB1 receptor is involved in ACEA-induced protective effects on neurons and mitochondrial functions, Sci. Rep., 5, 12440, 10.1038/srep12440

Szlavicz, 2015, Further Characterization of Hemopressin Peptide Fragments in the Opioid and Cannabinoid Systems, Anest. Analg., 121, 1488, 10.1213/ANE.0000000000000964

Zhang, 2015, Intracellular postsynaptic cannabinoid receptors link thyrotropin-releasing hormone receptors to TRPC-like channels in thalamic paraventricular nucleus neurons, Neuroscience, 311, 81, 10.1016/j.neuroscience.2015.10.015

Pan, 2015, Effects of neuropeptide FF and related peptides on the antinociceptive activities of VD-hemopressin(alpha) in naive and cannabinoid-tolerant mice, Eur. J. Pharmacol., 767, 119, 10.1016/j.ejphar.2015.10.016

Hasan, 2015, Curcumin and hemopressin treatment attenuates cholestasis-induced liver fibrosis in rats: Role of CB1 receptors, Naunyn Schmiedebergs Arch. Pharmacol., 389, 103

Cunha, 2008, Intracellular peptides as natural regulators of cell signaling, J. Biol. Chem., 283, 24448, 10.1074/jbc.M801252200

Russo, 2012, Natural intracellular peptides can modulate the interactions of mouse brain proteins and thimet oligopeptidase with 14-3-3epsilon and calmodulin, Proteomics, 12, 2641, 10.1002/pmic.201200032

Berti, 2012, Identification of intracellular peptides in rat adipose tissue: Insights into insulin resistance, Proteomics, 12, 2668, 10.1002/pmic.201200051

Fricker, 2012, Peptidomic analysis of HEK293T cells: Effect of the proteasome inhibitor epoxomicin on intracellular peptides, J. Proteom. Res., 11, 1981, 10.1021/pr2012076

Ribeiro, 2013, AGH is a new hemoglobin alpha-chain fragment with antinociceptive activity, Peptides, 48, 10, 10.1016/j.peptides.2013.07.011

Russo, 2014, A novel intracellular peptide derived from g1/s cyclin d2 induces cell death, J. Biol. Chem., 289, 16711, 10.1074/jbc.M113.537118

Russo, 2016, A Cyclin D2-derived peptide acts on specific cell cycle phases by activating ERK1/2 to cause the death of breast cancer cells, J. Proteom., 151, 24, 10.1016/j.jprot.2016.06.028

de Araujo, C.B., de Lima, L.P., Calderano, S.G., Damasceno, F.S., Silber, A.M., and Elias, M.C. (2019). Pep5, a fragment of cyclin D2, shows antiparasitic effects in different stages of the Trypanosoma cruzi life cycle and blocks parasite infectivity. Antimicrob. Agents Chemother.

Russo, 2016, EL28 is a novel intracellular peptide that activates immune proteasome and CD8+ T-cell response, J. Proteom., 16, S1874

Gelman, J.S., Sironi, J., Berezniuk, I., Dasgupta, S., Castro, L.M., Gozzo, F.C., Ferro, E.S., and Fricker, L.D. (2013). Alterations of the intracellular peptidome in response to the proteasome inhibitor bortezomib. PLoS ONE, 8.

Dasgupta, S., Fishman, M.A., Mahallati, H., Castro, L.M., Tashima, A.K., Ferro, E.S., and Fricker, L.D. (2015). Reduced Levels of Proteasome Products in a Mouse Striatal Cell Model of Huntington’s Disease. PLoS ONE, 10.

Morozov, 2018, Biological consequences of structural and functional proteasome diversity, Heliyon, 4, e00894, 10.1016/j.heliyon.2018.e00894

Russo, 2012, Inhibition of thimet oligopeptidase by siRNA alters specific intracellular peptides and potentiates isoproterenol signal transduction, FEBS Lett, 586, 3287, 10.1016/j.febslet.2012.07.002

Cavalcanti, 2014, Neurolysin knockout mice generation and initial phenotype characterization, J. Biol. Chem., 289, 15426, 10.1074/jbc.M113.539148

Castro, 2014, Peptidomic analysis of the neurolysin-knockout mouse brain, J. Proteom., 111, 238, 10.1016/j.jprot.2014.03.043

Ramachandran, 2017, A mammalian nervous-system-specific plasma membrane proteasome complex that modulates neuronal function, Nat. Struct. Mol. Biol., 24, 419, 10.1038/nsmb.3389

Mechoulam, 2014, Early phytocannabinoid chemistry to endocannabinoids and beyond, Nat. Rev. Neurosci., 15, 757, 10.1038/nrn3811

Wang, 2018, Antinociceptive effects of the endogenous cannabinoid peptide agonist VD-hemopressin(beta) in mice, Brain Res. Bull., 139, 48, 10.1016/j.brainresbull.2018.02.003

Zheng, 2017, CB1 cannabinoid receptor agonist mouse VD-hemopressin(alpha) produced supraspinal analgesic activity in the preclinical models of pain, Brain Res., 1680, 155, 10.1016/j.brainres.2017.12.013

Recinella, 2018, Effects of central RVD-hemopressin(alpha) administration on anxiety, feeding behavior and hypothalamic neuromodulators in the rat, Pharmacol. Rep., 70, 650, 10.1016/j.pharep.2018.01.010

Leone, 2017, Emotional disorders induced by Hemopressin and RVD-hemopressin(alpha) administration in rats, Pharmacol. Rep., 69, 1247, 10.1016/j.pharep.2017.06.010

Mechoulam, 1986, Interview with Prof. Raphael Mechoulam, codiscoverer of THC. Einstein, Int. J. Addict., 21, 579, 10.3109/10826088609083542

Mechoulam, 2010, [Endocannabinoids and psychiatric disorders: The road ahead], Braz J. Psychiatr., 32, S5

Mechoulam, 1970, Chemical basis of hashish activity, Science, 169, 611, 10.1126/science.169.3945.611

Blair, 2006, Activation of the cannabinoid type-1 receptor mediates the anticonvulsant properties of cannabinoids in the hippocampal neuronal culture models of acquired epilepsy and status epilepticus, J. Pharmacol. Exp. Ther., 317, 1072, 10.1124/jpet.105.100354

Jones, 2010, Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo, J. Pharmacol. Exp. Ther., 332, 569, 10.1124/jpet.109.159145

Shafaroodi, 2004, The interaction of cannabinoids and opioids on pentylenetetrazole-induced seizure threshold in mice, Neuropharmacology, 47, 390, 10.1016/j.neuropharm.2004.04.011

Wallace, 2002, Evidence for a physiological role of endocannabinoids in the modulation of seizure threshold and severity, Eur. J. Pharmacol., 452, 295, 10.1016/S0014-2999(02)02331-2

Hua, 2016, Crystal Structure of the Human Cannabinoid Receptor CB1, Cell, 167, 750, 10.1016/j.cell.2016.10.004

Hildebrandt, 2014, Efficient computation of root mean square deviations under rigid transformations, J. Comput. Chem., 35, 765, 10.1002/jcc.23513

Maiorov, 1994, Significance of root-mean-square deviation in comparing three-dimensional structures of globular proteins, J. Mol. Biol., 235, 625, 10.1006/jmbi.1994.1017

Turski, 1983, Limbic seizures produced by pilocarpine in rats: Behavioural, electroencephalographic and neuropathological study, Behav. Brain Res., 9, 315, 10.1016/0166-4328(83)90136-5

Rioli, 1998, Neuropeptide specificity and inhibition of recombinant isoforms of the endopeptidase 3.4.24.16 family: Comparison with the related recombinant endopeptidase 3.4.24.15, Biochem Biophys. Res. Commun., 250, 5, 10.1006/bbrc.1998.8941

Heimann, A.S., Gupta, A., Gomes, I., Rayees, R., Schlessinger, A., Ferro, E.S., Unterwald, E.M., and Devi, L.A. (2018). Generation of G protein-coupled receptor antibodies differentially sensitive to conformational states. PLoS ONE, 12.

Gupta, 2007, Conformation state-sensitive antibodies to G-protein-coupled receptors, J. Biol. Chem., 282, 5116, 10.1074/jbc.M609254200

Reckziegel, P., Festuccia, W.T., Britto, L.R.G., Jang, K.L.L., Romão, C.M., Heimann, J.C., Fogaça, M.V., Rodrigues, N.S., Silva, N.R., and Guimarães, F.S. (2017). A novel peptide that improves metabolic parameters without adverse central nervous system effects. Sci. Rep., 7.

Hershko, 1998, The ubiquitin system, Annu. Rev. Biochem., 67, 425, 10.1146/annurev.biochem.67.1.425

Groll, 1997, Structure of 20S proteasome from yeast at 2.4 A resolution, Nature, 386, 463, 10.1038/386463a0

Ciechanover, 2012, Non-canonical ubiquitin-based signals for proteasomal degradation, J. Cell Sci., 125, 539, 10.1242/jcs.093567

Goldberg, 2003, Protein degradation and protection against misfolded or damaged proteins, Nature, 426, 895, 10.1038/nature02263

Reits, 2003, Peptide diffusion, protection, and degradation in nuclear and cytoplasmic compartments before antigen presentation by MHC class I, Immunity, 18, 97, 10.1016/S1074-7613(02)00511-3

Kloetzel, 2001, Antigen processing by the proteasome, Nat. Rev. Mol. Cell. Biol., 2, 179, 10.1038/35056572

Kohler, 2001, The substrate translocation channel of the proteasome, Biochimie, 83, 325, 10.1016/S0300-9084(01)01242-1

Tian, 2011, An asymmetric interface between the regulatory and core particles of the proteasome, Nat. Struct. Mol. Biol., 18, 1259, 10.1038/nsmb.2147

Stumpf, 2008, Estimating the size of the human interactome, Proc. Natl. Acad. Sci. USA, 105, 6959, 10.1073/pnas.0708078105

Sanders, 2013, Transcriptome study of differential expression in schizophrenia, Hum. Mol. Genet., 22, 5001, 10.1093/hmg/ddt350

Fierz, 2011, Histone H2B ubiquitylation disrupts local and higher-order chromatin compaction, Nat. Chem. Biol., 7, 113, 10.1038/nchembio.501

Norbury, 1992, Animal cell cycles and their control, Annu. Rev. Biochem., 61, 441, 10.1146/annurev.bi.61.070192.002301

Malumbres, 2005, Mammalian cyclin-dependent kinases, Trends Biochem Sci, 30, 630, 10.1016/j.tibs.2005.09.005

Morgan, 1997, Cyclin-dependent kinases: Engines, clocks, and microprocessors, Annu. Rev. Cell Dev. Biol., 13, 261, 10.1146/annurev.cellbio.13.1.261

Ohtsubo, 1995, Human cyclin E, a nuclear protein essential for the G1-to-S phase transition, Mol. Cell. Biol., 15, 2612, 10.1128/MCB.15.5.2612

Hunter, 1994, Cyclins and cancer. II: Cyclin D and CDK inhibitors come of age, Cell, 79, 573, 10.1016/0092-8674(94)90543-6

Sherr, 1993, Mammalian G1 cyclins, Cell, 73, 1059, 10.1016/0092-8674(93)90636-5

Waclaw, 2004, Patterns of expression of cyclins A, B1, D, E and cdk 2 in preimplantation mouse embryos, Zygote, 12, 19, 10.1017/S0967199404002552

Qie, 2016, Cyclin D1, cancer progression, and opportunities in cancer treatment, J. Mol. Med. (Berl), 94, 1313, 10.1007/s00109-016-1475-3

Lecker, 2006, Protein degradation by the ubiquitin-proteasome pathway in normal and disease states, J. Am. Soc. Nephrol., 17, 1807, 10.1681/ASN.2006010083

Vodermaier, 2004, APC/C and SCF: Controlling each other and the cell cycle, Curr. Biol., 14, R787, 10.1016/j.cub.2004.09.020

Harper, 2002, The anaphase-promoting complex: it’s not just for mitosis any more, Genes Dev., 16, 2179, 10.1101/gad.1013102

Alao, 2007, The regulation of cyclin D1 degradation: Roles in cancer development and the potential for therapeutic invention, Mol. Cancer, 6, 24, 10.1186/1476-4598-6-24

Pagano, 1994, Cyclin D1-mediated inhibition of repair and replicative DNA synthesis in human fibroblasts, Genes Dev., 8, 1627, 10.1101/gad.8.14.1627

Sherr, 1999, CDK inhibitors: Positive and negative regulators of G1-phase progression, Genes Dev., 13, 1501, 10.1101/gad.13.12.1501

Degterev, 2005, Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury, Nat. Chem. Biol., 1, 112, 10.1038/nchembio711

Caserta, 2003, Q-VD-OPh, a broad spectrum caspase inhibitor with potent antiapoptotic properties, Apoptosis, 8, 345, 10.1023/A:1024116916932

Sodeoka, 2010, Development of selective inhibitors of necrosis, Chem. Rec., 10, 308, 10.1002/tcr.201000031

Suh, 2002, mtCLIC/CLIC4, an organellular chloride channel protein, is increased by DNA damage and participates in the apoptotic response to p53, Mol. Cell. Biol., 22, 3610, 10.1128/MCB.22.11.3610-3620.2002

Valenzuela, 2000, The nuclear chloride ion channel NCC27 is involved in regulation of the cell cycle, J. Physiol., 529, 541, 10.1111/j.1469-7793.2000.00541.x

Argenzio, 2016, Emerging biological roles of Cl- intracellular channel proteins, J. Cell Sci., 129, 4165, 10.1242/jcs.189795

Wang, 2014, Chloride intracellular channel 1 regulates colon cancer cell migration and invasion through ROS/ERK pathway, World J. Gastroenterol., 20, 2071, 10.3748/wjg.v20.i8.2071

Tian, 2014, Chloride intracellular channel 1 regulates prostate cancer cell proliferation and migration through the MAPK/ERK pathway, Cancer Biother. Radiopharm., 29, 339

Manso, 2016, Purification and Structural Analysis of Plectin and BPAG1e, Methods Enzymol., 569, 177, 10.1016/bs.mie.2015.05.002

Kazerounian, 2002, Unique role for the periplakin tail in intermediate filament association: Specific binding to keratin 8 and vimentin, Exp. Dermatol., 11, 428, 10.1034/j.1600-0625.2002.110506.x

Bausch, 2009, Plectin-1 is a biomarker of malignant pancreatic intraductal papillary mucinous neoplasms, J. Gastrointest. Surg., 13, 1948, 10.1007/s11605-009-1001-9

Bausch, 2011, Plectin-1 as a novel biomarker for pancreatic cancer, Clin. Cancer Res., 17, 302, 10.1158/1078-0432.CCR-10-0999

Katada, 2012, Plectin promotes migration and invasion of cancer cells and is a novel prognostic marker for head and neck squamous cell carcinoma, J. Proteom., 75, 1803, 10.1016/j.jprot.2011.12.018

Pawar, 2011, Quantitative tissue proteomics of esophageal squamous cell carcinoma for novel biomarker discovery, Cancer Biol. Ther., 12, 510, 10.4161/cbt.12.6.16833

Vallelian, 2015, Proteasome inhibition and oxidative reactions disrupt cellular homeostasis during heme stress, Cell Death Differ., 22, 597, 10.1038/cdd.2014.154

Fortes, 2012, Heme induces programmed necrosis on macrophages through autocrine TNF and ROS production, Blood, 119, 2368, 10.1182/blood-2011-08-375303

Baar, 2017, Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging, Cell, 169, 132, 10.1016/j.cell.2017.02.031

Ferreira, 2019, A selective inhibitor of mitofusin 1-betaIIPKC association improves heart failure outcome in rats, Nat. Commun., 10, 329, 10.1038/s41467-018-08276-6