Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Mol Cell
2016 Nov 03;643:507-519. doi: 10.1016/j.molcel.2016.09.010.
Show Gene links
Show Anatomy links
Cyclin F-Mediated Degradation of SLBP Limits H2A.X Accumulation and Apoptosis upon Genotoxic Stress in G2.
Dankert JF
,
Rona G
,
Clijsters L
,
Geter P
,
Skaar JR
,
Bermudez-Hernandez K
,
Sassani E
,
Fenyö D
,
Ueberheide B
,
Schneider R
,
Pagano M
.
???displayArticle.abstract??? SLBP (stem-loop binding protein) is a highly conserved factor necessary for the processing, translation, and degradation of H2AFX and canonical histone mRNAs. We identified the F-box protein cyclin F, a substrate recognition subunit of an SCF (Skp1-Cul1-F-box protein) complex, as the G2 ubiquitin ligase for SLBP. SLBP interacts with cyclin F via an atypical CY motif, and mutation of this motif prevents SLBP degradation in G2. Expression of an SLBP stable mutant results in increased loading of H2AFX mRNA onto polyribosomes, resulting in increased expression of H2A.X (encoded by H2AFX). Upon genotoxic stress in G2, high levels of H2A.X lead to persistent γH2A.X signaling, high levels of H2A.X phosphorylated on Tyr142, high levels of p53, and induction of apoptosis. We propose that cyclin F co-evolved with the appearance of stem-loops in vertebrate H2AFX mRNA to mediate SLBP degradation, thereby limiting H2A.X synthesis and cell death upon genotoxic stress.
Atsumi,
ATM and SIRT6/SNF2H Mediate Transient H2AX Stabilization When DSBs Form by Blocking HUWE1 to Allow Efficient γH2AX Foci Formation.
2015, Pubmed
Atsumi,
ATM and SIRT6/SNF2H Mediate Transient H2AX Stabilization When DSBs Form by Blocking HUWE1 to Allow Efficient γH2AX Foci Formation.
2015,
Pubmed
Bai,
SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box.
1996,
Pubmed
Bonner,
Histone H2A.X gene transcription is regulated differently than transcription of other replication-linked histone genes.
1993,
Pubmed
Brodersen,
CRL4(WDR23)-Mediated SLBP Ubiquitylation Ensures Histone Supply during DNA Replication.
2016,
Pubmed
Brooks,
A multiprotein occupancy map of the mRNP on the 3' end of histone mRNAs.
2015,
Pubmed
Cakmakci,
SLIP1, a factor required for activation of histone mRNA translation by the stem-loop binding protein.
2008,
Pubmed
,
Xenbase
Choe,
Rapid degradation of replication-dependent histone mRNAs largely occurs on mRNAs bound by nuclear cap-binding proteins 80 and 20.
2013,
Pubmed
Choe,
The mRNP remodeling mediated by UPF1 promotes rapid degradation of replication-dependent histone mRNA.
2014,
Pubmed
Clarkson,
Regions of variant histone His2AvD required for Drosophila development.
1999,
Pubmed
,
Xenbase
Cook,
Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions.
2009,
Pubmed
D'Angiolella,
SCF(Cyclin F) controls centrosome homeostasis and mitotic fidelity through CP110 degradation.
2010,
Pubmed
D'Angiolella,
Cyclin F-mediated degradation of ribonucleotide reductase M2 controls genome integrity and DNA repair.
2012,
Pubmed
Djakbarova,
DDB1 and CUL4 associated factor 11 (DCAF11) mediates degradation of Stem-loop binding protein at the end of S phase.
2016,
Pubmed
Dominski,
Stem-loop binding protein facilitates 3'-end formation by stabilizing U7 snRNP binding to histone pre-mRNA.
1999,
Pubmed
Dong,
H2AX phosphorylation regulated by p38 is involved in Bim expression and apoptosis in chronic myelogenous leukemia cells induced by imatinib.
2014,
Pubmed
Elia,
Quantitative Proteomic Atlas of Ubiquitination and Acetylation in the DNA Damage Response.
2015,
Pubmed
Emanuele,
Global identification of modular cullin-RING ligase substrates.
2011,
Pubmed
Erkmann,
Nuclear import of the stem-loop binding protein and localization during the cell cycle.
2005,
Pubmed
Fuchs,
MEKK1/JNK signaling stabilizes and activates p53.
1998,
Pubmed
Gallie,
The histone 3'-terminal stem-loop is necessary for translation in Chinese hamster ovary cells.
1996,
Pubmed
Giono,
The RNA Response to DNA Damage.
2016,
Pubmed
Gruosso,
Chronic oxidative stress promotes H2AX protein degradation and enhances chemosensitivity in breast cancer patients.
2016,
Pubmed
Harper,
The DNA damage response: ten years after.
2007,
Pubmed
Kari,
A subset of histone H2B genes produces polyadenylated mRNAs under a variety of cellular conditions.
2013,
Pubmed
Kaygun,
Regulated degradation of replication-dependent histone mRNAs requires both ATR and Upf1.
2005,
Pubmed
Klein,
Cyclin F suppresses B-Myb activity to promote cell cycle checkpoint control.
2015,
Pubmed
Kodama,
The stem-loop binding protein CDL-1 is required for chromosome condensation, progression of cell death and morphogenesis in Caenorhabditis elegans.
2002,
Pubmed
Kolev,
Symplekin and multiple other polyadenylation factors participate in 3'-end maturation of histone mRNAs.
2005,
Pubmed
,
Xenbase
Koseoglu,
Phosphorylation of threonine 61 by cyclin a/Cdk1 triggers degradation of stem-loop binding protein at the end of S phase.
2008,
Pubmed
Lanzotti,
Drosophila stem-loop binding protein intracellular localization is mediated by phosphorylation and is required for cell cycle-regulated histone mRNA expression.
2004,
Pubmed
Lu,
Cell apoptosis: requirement of H2AX in DNA ladder formation, but not for the activation of caspase-3.
2006,
Pubmed
Madigan,
DNA double-strand break-induced phosphorylation of Drosophila histone variant H2Av helps prevent radiation-induced apoptosis.
2002,
Pubmed
Marzluff,
Metabolism and regulation of canonical histone mRNAs: life without a poly(A) tail.
2008,
Pubmed
Mullen,
Degradation of histone mRNA requires oligouridylation followed by decapping and simultaneous degradation of the mRNA both 5' to 3' and 3' to 5'.
2008,
Pubmed
Romeo,
CstF64: cell cycle regulation and functional role in 3' end processing of replication-dependent histone mRNAs.
2014,
Pubmed
Saha,
Targeting p53 via JNK pathway: a novel role of RITA for apoptotic signaling in multiple myeloma.
2012,
Pubmed
Sharma,
A p27Kip1 mutant that does not inhibit CDK activity promotes centrosome amplification and micronucleation.
2012,
Pubmed
Stucki,
Histone H2A.X Tyr142 phosphorylation: a novel sWItCH for apoptosis?
2009,
Pubmed
Sullivan,
Drosophila stem loop binding protein coordinates accumulation of mature histone mRNA with cell cycle progression.
2001,
Pubmed
,
Xenbase
Swaminathan,
The role of histone H2Av variant replacement and histone H4 acetylation in the establishment of Drosophila heterochromatin.
2005,
Pubmed
Taneja,
Histone H2AX phosphorylation as a predictor of radiosensitivity and target for radiotherapy.
2004,
Pubmed
Townley-Tilson,
Genome-wide analysis of mRNAs bound to the histone stem-loop binding protein.
2006,
Pubmed
Updike,
Temporal regulation of foregut development by HTZ-1/H2A.Z and PHA-4/FoxA.
2006,
Pubmed
Wagner,
ZFP100, a component of the active U7 snRNP limiting for histone pre-mRNA processing, is required for entry into S phase.
2006,
Pubmed
Walter,
SCF(Cyclin F)-dependent degradation of CDC6 suppresses DNA re-replication.
2016,
Pubmed
Whittle,
The genomic distribution and function of histone variant HTZ-1 during C. elegans embryogenesis.
2008,
Pubmed
Yoshida,
A comprehensive method for detecting ubiquitinated substrates using TR-TUBE.
2015,
Pubmed
Young,
TIMELESS Forms a Complex with PARP1 Distinct from Its Complex with TIPIN and Plays a Role in the DNA Damage Response.
2015,
Pubmed
Zheng,
Phosphorylation of stem-loop binding protein (SLBP) on two threonines triggers degradation of SLBP, the sole cell cycle-regulated factor required for regulation of histone mRNA processing, at the end of S phase.
2003,
Pubmed
,
Xenbase
van Daal,
A histone variant, H2AvD, is essential in Drosophila melanogaster.
1992,
Pubmed
