EIF3F (eukaryotic translation initiation factor 3, subunit F)

2009-07-01   Jiaqi Shi , Mark A Nelson 

Department of Surgery, Arizona Cancer Center, University of Arizona, USA (JS); Department of Pathology, Arizona Cancer Center, University of Arizona, USA (JS, MN)

Identity

HGNC
LOCATION
11p15.4
LOCUSID
ALIAS
EIF3S5,MRT67,eIF3-p47

DNA/RNA

Description

10.82kb long.

Transcription

8 exons; transcript length: 3,228 bps; 1073 bp coding sequence.

Pseudogene

Chromosome 2 from 58,332,079 to 58,333,164 bp (AC007250.3, Ensembl).

Proteins

Description

357 amino acids; 37,563.75 Da; Isoelectric point: 5.122; Mov34/MPN/PAD1 domain.

Expression

Ubiquitous.

Localisation

Cytoplasmic. There is also evidence of its existence in the nucleus.

Function

eIF3f is a subunit of eIF3 complex and is highly conserved among species. eIF3f interacts with the caspase-processed isoform of CDK11 (CDK11p46), which appears to be a down-stream effector in apoptotic signaling. eIF3f can be phosphorylated at Ser46 and Thr119 by CDK11p46 during apoptosis. The phosphorylation of eIF3f contributes to translation inhibition and apoptosis. The expression of eIF3f is significantly decreased in pancreatic cancer and melanoma. Loss of the eIF3f allele has been reported in pancreatic cancer and melanoma. Ectopic expression of eIF3f causes rRNA degradation, inhibits translation and cell proliferation, and induces apoptosis in pancreatic cancer and melanoma cells. On the other hand, knockdown of eIF3f prevents apoptosis in pancreatic cancer and melanoma cells. Recent studies also showed decreased cell growth, cell proliferation, colony formation and increased apoptosis in eIF3f-overexpressing NIH3T3 cells.

Homology

eIF3f is not found in S. cerevisiae; However it is found in Schizosaccharomyces pombe (SPBC4C3.07, 35% identity) and in Drosophila Melanogaster (CG9769, 49% identity).

Mutations

Note

No eIF3f mutations have been reported.

Implicated in

Entity name
Pancreatic cancer
Disease
Decreased eIF3f mRNA and protein was found in pancreatic cancer.
Oncogenesis
Decreased eIF3f gene expression may result from loss of eIF3f gene allele and down regulation of transcription. Overexpression of eIF3f in pancreatic cancer and melanoma cells can lead to 28S rRNA degradation, decreased translation and increased apoptosis. On the other hand, knockdown of eIF3f attenuates apoptosis in tumor cells.
Entity name
Melanoma
Disease
Decreased eIF3f mRNA and protein was found in melanoma.
Oncogenesis
See above
Entity name
Muscle atrophy
Disease
eIF3f is a key target of MAFbx, an E3 ubiquitin ligase, during muscle atrophy and has a major role in skeletal muscle hypertrophy. During muscle atrophy, MAFbx targets eIF3f for ubiquitination and degradation. Thus, eIF3f appears to be an attractive therapeutic target.

Bibliography

Pubmed IDLast YearTitleAuthors
183815852008Loss of the eukaryotic initiation factor 3f in melanoma.Doldan A et al
186581242008All translation elongation factors and the e, f, and h subunits of translation initiation factor 3 are encoded by 5'-terminal oligopyrimidine (TOP) mRNAs.Iadevaia V et al
192895982009mRNA retrotransposition coupled with 5' inversion as a possible source of new genes.Kojima KK et al
183544982008The initiation factor eIF3-f is a major target for atrogin1/MAFbx function in skeletal muscle atrophy.Lagirand-Cantaloube J et al
175816322007Reconstitution reveals the functional core of mammalian eIF3.Masutani M et al
124466802003The p34cdc2-related cyclin-dependent kinase 11 interacts with the p47 subunit of eukaryotic initiation factor 3 during apoptosis.Shi J et al
192458112009Phosphorylation of the eukaryotic initiation factor 3f by cyclin-dependent kinase 11 during apoptosis.Shi J et al
165320222006Decreased expression of eukaryotic initiation factor 3f deregulates translation and apoptosis in tumor cells.Shi J et al
192375692009Inhibition of HIV-1 replication by eIF3f.Valente ST et al

Other Information

Locus ID:

NCBI: 8665
MIM: 603914
HGNC: 3275
Ensembl: ENSG00000175390

Variants:

dbSNP: 8665
ClinVar: 8665
TCGA: ENSG00000175390
COSMIC: EIF3F

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000175390ENST00000531329E9PQV8
ENSG00000175390ENST00000531572H0YDT6
ENSG00000175390ENST00000533626O00303
ENSG00000175390ENST00000640290A0A1W2PP79
ENSG00000175390ENST00000651655O00303

Expression (GTEx)

0
50
100
150

Pathways

PathwaySourceExternal ID
RNA transportKEGGko03013
RNA transportKEGGhsa03013
Metabolism of proteinsREACTOMER-HSA-392499
TranslationREACTOMER-HSA-72766
Eukaryotic Translation InitiationREACTOMER-HSA-72613
Cap-dependent Translation InitiationREACTOMER-HSA-72737
Formation of a pool of free 40S subunitsREACTOMER-HSA-72689
Formation of the ternary complex, and subsequently, the 43S complexREACTOMER-HSA-72695
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43SREACTOMER-HSA-72662
Translation initiation complex formationREACTOMER-HSA-72649
Ribosomal scanning and start codon recognitionREACTOMER-HSA-72702
GTP hydrolysis and joining of the 60S ribosomal subunitREACTOMER-HSA-72706
L13a-mediated translational silencing of Ceruloplasmin expressionREACTOMER-HSA-156827
Gene ExpressionREACTOMER-HSA-74160

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
211248832010The translation initiation factor 3f (eIF3f) exhibits a deubiquitinase activity regulating Notch activation.32
179181922008Loss of the eukaryotic initiation factor 3f in pancreatic cancer.28
192458112009Phosphorylation of the eukaryotic initiation factor 3f by cyclin-dependent kinase 11 during apoptosis.26
198541362009HIV-1 mRNA 3' end processing is distinctively regulated by eIF3f, CDK11, and splice factor 9G8.26
192375692009Inhibition of HIV-1 replication by eIF3f.23
183815852008Loss of the eukaryotic initiation factor 3f in melanoma.22
224578252012The tumor suppressive role of eIF3f and its function in translation inhibition and rRNA degradation.19
247326442014Expression of eukaryotic initiation factor 3f is associated with prognosis in gastric carcinomas.7
269889172016eIF3f reduces tumor growth by directly interrupting clusterin with anti-apoptotic property in cancer cells.6
246788902014Decreased expression of eukaryotic initiation factor 3f is an adverse prognostic factor for stage I-III gastric cancer.4

Citation

Jiaqi Shi ; Mark A Nelson

EIF3F (eukaryotic translation initiation factor 3, subunit F)

Atlas Genet Cytogenet Oncol Haematol. 2009-07-01

Online version: http://atlasgeneticsoncology.org/gene/44407/eif3f