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EIF3C (eukaryotic translation initiation factor 3, subunit C)

Identity

Other namesEIF3S8
eIF3-p110
eIF3 subunit p110
p110
Hugo EIF3C
Location 16p11.2
Note eIF3c is one of 12 subunit proteins comprising the eukaryotic initiation factor 3 (eIF3) complex.

DNA/RNA

Description The EIF3C gene is composed of 21 exons. No alternative splicing has been reported for eIF3c.
The EIF3C gene is located on chromosome 16p11.2 within an unstable region prone to duplication, and intact duplication of the entire EIF3C gene has been demonstrated in multiple tissue types. One mechanism of eIF3c overexpression, observed in various tumor types, may be gene duplication.

Protein

 
  Schematic of the 913 amino acid eIF3c protein with amino acid positions shown and locations of the PCI domain. Also indicated are the known minimal regions in eIF3c required for binding by interacting proteins. These include eIF complexes eIF1 and eIF5, the NF2 tumor suppressor merlin, and murine viral stress mediated inhibitors of protein translation MuP56 and MuP54. For merlin, the broken line indicates a region promoting stronger merlin binding when included. Note that eIF3c also binds the COP9 signalosome protein CSN7 in Arabidopsis, which may mediate inhibition of protein translation.
Description The eIF3c protein is 913 amino acids in length. The eIF3c protein possesses the PCI (proteasome component region) domain within its C-terminal half (also referred to as PINT domain). Domain searching reveals that EIF3c also possesses a winged helix repressor DNA-binding domain overlapping with the PCI domain.
Expression Ubiquitous.
Localisation eIF3c is cytoplasmic. There is some evidence of eIF3c occurring in the nucleus consistent with reports of intranuclear protein translation as well as regulation of protein translation by interaction with the COP9 signalosome.
Function The initiation of protein translation is a complex sequence of events mediated by the interaction of eIF3 with phosphorylated mTOR . Multiple interactions by eIF3 subsequently take place during the progression of protein translation initiation including the proper positioning of the preinitiation complex on the 40S ribosome mediated by eIF3. EIF3c has a significant role in binding to two AUG recognition factors, eIF1 and eIF5, and these interactions are required for proper AUG scanning by the preinitiation complex.
EIF3c is overexpressed in some tumors including seminomas and meningiomas. EIF3c can also interact with the neurofibromatosis 2 (NF2) tumor suppressor merlin (schwannomin) and merlin can inhibit eIF3c mediated cell proliferation. In meningiomas eIF3c expression was inversely related to merlin expression and was overexpressed in meningiomas that had lost merlin expression. EIF3c overexpression can also transform NIH/3T3 fibroblasts, indicated by decreased doubling times, increased clonogenicity, increased viability, facilitated S-phase entry, attenuated apoptosis, formation of transformed foci, and anchorage-independent growth.
Murine EIF3c is also a target of inhibitory proteins induced by viral stress. Viral induced MuP56 and MuP54 bind eIF3c in different locations resulting in protein translation inhibition.
In Arabidopsis, eIF3c also interacts with the COP9 signalosome subunit CSN7 in the nucleus. COP9 binding is thought to be associated with downregulated protein translation. eIF3c possesses the PCI domain common among proteasome member proteins and also found in other eIF subunit proteins.
Homology eIF3c is the homolog to yeast NIP1 (37% identity).

Mutations

Note No eIF3c mutations have been reported.

Implicated in

Entity Various Cancer
Oncogenesis eIF3c has been noted overexpressed in a subset of testicular tumors (seminomas). EIF3c has also been shown overexpressed in meningiomas that have lost expression of the neurofibromatosis 2 tumor suppressor merlin (approximately 50% of sporadic meningiomas).
  

To be noted

eIF3c is an oncoprotein overexpressed in tumors. As such eIF3c is a potential therapeutic target. eIF3c may be a particularly good therapeutic target for NF2 since all tumors that had lost merlin function had overexpressed eIF3c.

External links

Nomenclature
HugoEIF3S8
GDBEIF3C
Entrez_GeneEIF3C  8663  eukaryotic translation initiation factor 3, subunit C
Cards
AtlasEIF3CID44187ch16p11
GeneCardsEIF3C
EnsemblEIF3C [Search_View]   ENSG00000184110 [Gene_View]
GenatlasEIF3C
GeneLynxEIF3C
eGenomeEIF3C
euGene8663
Genomic and cartography
GoldenPathEIF3C  -  16p11.2   chr16:28630283-28654549 +  16p11.2   [Description]    (hg18-Mar_2006)
EnsemblEIF3C - 16p11.2 [CytoView]
NCBIMapview
OMIMDisease map [OMIM]
HomoloGeneEIF3C
Gene and transcription
GenbankAK000739 [ ENTREZ ]
GenbankAK055366 [ ENTREZ ]
GenbankAK130531 [ ENTREZ ]
GenbankAY762099 [ ENTREZ ]
GenbankBC000533 [ ENTREZ ]
RefSeqNM_001037808 [ SRS ]    NM_001037808 [ ENTREZ ]
RefSeqNM_003752 [ SRS ]    NM_003752 [ ENTREZ ]
RefSeqAC_000059 [ SRS ]    AC_000059 [ ENTREZ ]
RefSeqNC_000016 [ SRS ]    NC_000016 [ ENTREZ ]
RefSeqNT_010393 [ SRS ]    NT_010393 [ ENTREZ ]
RefSeqNW_926284 [ SRS ]    NW_926284 [ ENTREZ ]
AceViewEIF3C AceView - NCBI
UnigeneHs.567374 [ SRS ]    Hs.567374 [ NCBI ]     HS567374 [ spliceNest ]
Protein : pattern, domain, 3D structure
SwissProtQ99613 [ SRS]    Q99613 [ EXPASY ]     Q99613 [ INTERPRO ]
InterproIPR008905 eIF3c_N [ SRS ]    IPR008905 eIF3c_N [ EBI ]
InterproIPR000717 PCI [ SRS ]    IPR000717 PCI [ EBI ]
InterproIPR011991 Wing_hlx_DNA_bd [ SRS ]    IPR011991 Wing_hlx_DNA_bd [ EBI ]
CluSTrQ99613
PfamPF05470 eIF-3c_N [ SRS ]    PF05470 eIF-3c_N [ Sanger ]    pfam05470 [ NCBI-CDD ]
PfamPF01399 PCI [ SRS ]    PF01399 PCI [ Sanger ]    pfam01399 [ NCBI-CDD ]
SmartSM00088 PINT [EMBL]
BlocksQ99613
HPRD04889
Protein Interaction databases
DIPQ99613
IntActQ99613
Polymorphism : SNP, mutations, diseases
OMIM603916    [ map ]   
GENECLINICS603916
SNPEIF3C [dbSNP-NCBI]  
SNPNM_001037808 [SNP-NCI]  
SNPNM_003752 [SNP-NCI]  
SNPEIF3C [GeneSNPs - Utah]  EIF3C] [HGBASE - SRS]
HAPMAPEIF3C [HAPMAP]  
HGMDEIF3S8
General knowledge
Family BrowserEIF3C [UCSC Family Browser]
SOURCENM_001037808
SOURCENM_003752
SMDHs.567374
SAGEHs.567374
GOtranslation initiation factor activity [Amigo]  translation initiation factor activity
GOtranslation initiation factor activity [Amigo]  translation initiation factor activity
GOeukaryotic translation initiation factor 3 complex [Amigo]  eukaryotic translation initiation factor 3 complex
GOeukaryotic translation initiation factor 3 complex [Amigo]  eukaryotic translation initiation factor 3 complex
GOtranslational initiation [Amigo]  translational initiation
GOregulation of translational initiation [Amigo]  regulation of translational initiation
PubGeneEIF3C
TreeFamEIF3S8
CTD8663 [Comparative ToxicoGenomics Database]
Other databases
Probes
ProbeEIF3C Related clones (RZPD - Berlin)
PubMed
PubMed19 Pubmed reference(s) in LocusLink

Bibliography

Conservation and diversity of eukaryotic translation initiation factor eIF3.
Asano K, Kinzy TG, Merrick WC, Hershey JW
The Journal of biological chemistry. 1997 ; 272 (2) : 1101-1109.
PMID 8995409
 
Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q.
Loftus BJ, Kim UJ, Sneddon VP, Kalush F, Brandon R, Fuhrmann J, Mason T, Crosby ML, Barnstead M, Cronin L, Deslattes Mays A, Cao Y, Xu RX, Kang HL, Mitchell S, Eichler EE, Harris PC, Venter JC, Adams MD
Genomics. 1999 ; 60 (3) : 295-308.
PMID 10493829
 
Eukaryotic initiation factor 3 p110 mRNA is overexpressed in testicular seminomas.
Rothe M, Ko Y, Albers P, Wernert N
The American journal of pathology. 2000 ; 157 (5) : 1597-1604.
PMID 11073819
 
Arabidopsis eIF3e (INT-6) associates with both eIF3c and the COP9 signalosome subunit CSN7.
Yahalom A, Kim TH, Winter E, Karniol B, von Arnim AG, Chamovitz DA
The Journal of biological chemistry. 2001 ; 276 (1) : 334-340.
PMID 11029466
 
A method for the rapid construction of cRNA standard curves in quantitative real-time reverse transcription polymerase chain reaction.
Fronhoffs S, Totzke G, Stier S, Wernert N, Rothe M, Brˆºning T, Koch B, Sachinidis A, Vetter H, Ko Y
Molecular and cellular probes. 2002 ; 16 (2) : 99-110.
PMID 12030760
 
The yeast eukaryotic initiation factor 4G (eIF4G) HEAT domain interacts with eIF1 and eIF5 and is involved in stringent AUG selection.
He H, von der Haar T, Singh CR, Ii M, Li B, Hinnebusch AG, McCarthy JE, Asano K
Molecular and cellular biology. 2003 ; 23 (15) : 5431-5445.
PMID 12861028
 
Induction and mode of action of the viral stress-inducible murine proteins, P56 and P54.
Terenzi F, Pal S, Sen GC
Virology. 2005 ; 340 (1) : 116-124.
PMID 16023166
 
eIF3: a versatile scaffold for translation initiation complexes.
Hinnebusch AG
Trends in biochemical sciences. 2006 ; 31 (10) : 553-562.
PMID 16920360
 
Schwannomin inhibits tumorigenesis through direct interaction with the eukaryotic initiation factor subunit c (eIF3c).
Scoles DR, Yong WH, Qin Y, Wawrowsky K, Pulst SM
Human molecular genetics. 2006 ; 15 (7) : 1059-1070.
PMID 16497727
 
Individual overexpression of five subunits of human translation initiation factor eIF3 promotes malignant transformation of immortal fibroblast cells.
Zhang L, Pan X, Hershey JW
The Journal of biological chemistry. 2007 ; 282 (8) : 5790-5800.
PMID 17170115
 
The merlin interacting proteins reveal multiple targets for NF2 therapy.
Scoles DR
Biochimica et biophysica acta. 2008 ; 1785 (1) : 32-54.
PMID 17980164
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written02-2008Daniel R Scoles
Division of Neurology, CSMC Burns and Allen Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 9, USA

Citation

This paper should be referenced as such :
Scoles Daniel R . EIF3C (eukaryotic translation initiation factor 3, subunit C). Atlas Genet Cytogenet Oncol Haematol. February 2008 .
URL : http://AtlasGeneticsOncology.org/Genes/EIF3CID44187ch16p11.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Jul 2 08:23:14 2008


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