Beyond the walls of the nucleus: the role of histones in cellular signaling and innate immunity

被引:135
作者
Parseghian, Missag H. [1 ]
Luhrs, Keith A. [1 ]
机构
[1] Peregrine Pharmaceut Inc, Res & Dev, Tustin, CA 92780 USA
关键词
histone; histone H1; innate immunity; antimicrobial peptides; necrosis; antibody therapeutics; autoimmune disease; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CHICK ERYTHROCYTE NUCLEI; VS. INACTIVE CHROMATIN; SOMATIC H1 SUBTYPES; LIVING HUMAN-CELLS; C-TERMINAL DOMAIN; IN-VIVO; ANTIMICROBIAL PEPTIDE; CUTANEOUS LEISHMANIASIS; GENE-EXPRESSION;
D O I
10.1139/O06-082
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Although they are one of the oldest family of proteins known (first described in 1884 by Kossel), histones continue to surprise researchers with their ever expanding roles in biology. In the past 25 years, the view of core histone octamers as a simple spool around which DNA in the nucleus is wound and linker histones as mere fasteners clipping it all together has transformed into the realization that histones play a vital role in transcriptional regulation. Through post-translational modifications, histones control the accessibility of transcription factors and a host of other proteins to multiple, conceivably thousands of, genes at once. While researchers have spent decades deciphering the role of histones in the overall structure of chromatin, it might surprise some to find that an entirely separate faction of scientists have focused on the role of histones beyond the confines of the nuclear envelope. In the past decade, there has been an accumulation of observations that suggest that histones can be found at the mitochondrion during the onset of apoptotic signaling and even at the cell surface, acting as a receptor for bacterial and viral proteins. More provocatively, immunologists are becoming convinced that they can also be found in the lumen of several tissues, acting as antimicrobial agents-critical components of an ancient innate immune system. Perhaps nowhere is this observation as dramatic as in the ability of neutrophils to entrap bacterial pathogens by casting out "nets" of DNA and histones that not only act as a physical barrier, but also display bactericidal activity. As our views regarding the role of histones inside and outside the cell evolve, some have begun to develop therapies that either utilize or target histones in the fight against cancer, microbial infection, and autoimmune disease. It is our goal here to begin the process of merging the dichotomous lives of histones both within and without the nuclear membrane.
引用
收藏
页码:589 / 604
页数:16
相关论文
共 111 条
[1]   Mammalian linker-histone subtypes differentially affect gene expression in vivo [J].
Alami, R ;
Fan, YH ;
Pack, S ;
Sonbuchner, TM ;
Besse, A ;
Lin, QC ;
Greally, JM ;
Skouitchi, AL ;
Bouhassira, EE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (10) :5920-5925
[2]  
Anderson PM., 2003, Cancer Therapy, V1, P297
[3]   KINETICS OF PROTEIN UPTAKE BY CHICK ERYTHROCYTE NUCLEI DURING REACTIVATION IN CHICK-MAMMALIAN HETEROKARYONS [J].
APPELS, R ;
BOLUND, L ;
GOTO, S ;
RINGERTZ, NR .
EXPERIMENTAL CELL RESEARCH, 1974, 85 (01) :182-190
[4]   BIOCHEMICAL ANALYSIS OF REACTIVATED CHICK ERYTHROCYTE NUCLEI ISOLATED FROM CHICK HELA HETEROKARYONS [J].
APPELS, R ;
BOLUND, L ;
RINGERTZ, NR .
JOURNAL OF MOLECULAR BIOLOGY, 1974, 87 (02) :339-&
[5]   Development of autoantibodies before the clinical onset of systemic lupus erythematosus [J].
Arbuckle, MR ;
McClain, MT ;
Rubertone, MV ;
Scofield, RH ;
Dennis, GJ ;
James, JA ;
Harley, JB .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 349 (16) :1526-1533
[6]   Significant (re)location: how to use chromatin and/or abundant proteins as messages of life and death [J].
Bianchi, ME .
TRENDS IN CELL BIOLOGY, 2004, 14 (06) :287-293
[7]   Rabbit anti-HMG-17 antibodies recognize similar epitopes on the HMG-17 molecule as lupus autoantibodies. Relation with histone H1 defined epitopes [J].
Boumba, VA ;
Seferiadis, K .
JOURNAL OF PEPTIDE SCIENCE, 2002, 8 (12) :683-694
[8]   Neutrophil extracellular traps kill bacteria [J].
Brinkmann, V ;
Reichard, U ;
Goosmann, C ;
Fauler, B ;
Uhlemann, Y ;
Weiss, DS ;
Weinrauch, Y ;
Zychlinsky, A .
SCIENCE, 2004, 303 (5663) :1532-1535
[9]   Extracellularly occurring histone H1 mediates the binding of thyroglobulin to the cell surface of mouse macrophages [J].
Brix, K ;
Summa, W ;
Lottspeich, F ;
Herzog, V .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (02) :283-293
[10]   Differential effect of H1 variant overexpression on cell cycle progression and gene expression [J].
Brown, DT ;
Alexander, BT ;
Sittman, DB .
NUCLEIC ACIDS RESEARCH, 1996, 24 (03) :486-493