Gene Section - Inist

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Gene Section Mini Review

EIF3F (eukaryotic translation initiation factor 3, subunit F) 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, MAN) Published in Atlas Database: July 2009 Online updated version : http://AtlasGeneticsOncology.org/Genes/EIF3FID44407ch11p15.html DOI: 10.4267/2042/44774 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2010 Atlas of Genetics and Cytogenetics in Oncology and Haematology

Function

Identity

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 eIF3foverexpressing NIH3T3 cells.

Other names: EIF3S5; eIF-3-epsilon; eIF3-epsilon; eIF3-p47; eIF3f; eIF3 subunit p47; p47 HGNC (Hugo): EIF3F Location: 11p15.4 Note: eIF3f is one of at least 13 subunits comprising the eukaryotic initiation factor 3 (eIF3) complex.

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).

Homology

Protein

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).

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

Mutations

Expression Ubiquitous.

Note No eIF3f mutations have been reported.

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

Atlas Genet Cytogenet Oncol Haematol. 2010; 14(6)

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EIF3F (eukaryotic translation initiation factor 3, subunit F)

Shi J, Nelson MA

Implicated in

References

Pancreatic cancer

Shi J, Feng Y, Goulet AC, Vaillancourt RR, Sachs NA, Hershey JW, Nelson MA. The p34cdc2-related cyclin-dependent kinase 11 interacts with the p47 subunit of eukaryotic initiation factor 3 during apoptosis. J Biol Chem. 2003 Feb 14;278(7):5062-71

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.

Shi J, Kahle A, Hershey JW, Honchak BM, Warneke JA, Leong SP, Nelson MA. Decreased expression of eukaryotic initiation factor 3f deregulates translation and apoptosis in tumor cells. Oncogene. 2006 Aug 10;25(35):4923-36 Masutani M, Sonenberg N, Yokoyama S, Imataka H. Reconstitution reveals the functional core of mammalian eIF3. EMBO J. 2007 Jul 25;26(14):3373-83 Doldan A, Chandramouli A, Shanas R, Bhattacharyya A, Cunningham JT, Nelson MA, Shi J. Loss of the eukaryotic initiation factor 3f in pancreatic cancer. Mol Carcinog. 2008 Mar;47(3):235-44

Melanoma

Doldan A, Chandramouli A, Shanas R, Bhattacharyya A, Leong SP, Nelson MA, Shi J. Loss of the eukaryotic initiation factor 3f in melanoma. Mol Carcinog. 2008 Oct;47(10):806-13

Disease Decreased eIF3f mRNA and protein was found in melanoma. Oncogenesis See above.

Iadevaia V, Caldarola S, Tino E, Amaldi F, Loreni F. All translation elongation factors and the e, f, and h subunits of translation initiation factor 3 are encoded by 5'-terminal oligopyrimidine (TOP) mRNAs. RNA. 2008 Sep;14(9):1730-6 Lagirand-Cantaloube J, Offner N, Csibi A, Leibovitch MP, Batonnet-Pichon S, Tintignac LA, Segura CT, Leibovitch SA. The initiation factor eIF3-f is a major target for atrogin1/MAFbx function in skeletal muscle atrophy. EMBO J. 2008 Apr 23;27(8):1266-76

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.

Kojima KK, Okada N. mRNA retrotransposition coupled with 5' inversion as a possible source of new genes. Mol Biol Evol. 2009 Jun;26(6):1405-20 Shi J, Hershey JW, Nelson MA. Phosphorylation of the eukaryotic initiation factor 3f by cyclin-dependent kinase 11 during apoptosis. FEBS Lett. 2009 Mar 18;583(6):971-7

To be noted

Valente ST, Gilmartin GM, Mott C, Falkard B, Goff SP. Inhibition of HIV-1 replication by eIF3f. Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4071-8

Note eIF3f is a potential tumor suppressor in pancreatic cancer and melanoma. Loss of heterozygosity and decreased expression of eIF3f has been found in most human pancreatic cancer and melanoma specimens. Silencing of eIF3f increases cell proliferation and colony formation. Restoration of eIF3f expression induces cancer cell death.

Atlas Genet Cytogenet Oncol Haematol. 2010; 14(6)

This article should be referenced as such: Shi J, Nelson MA. EIF3F (eukaryotic translation initiation factor 3, subunit F). Atlas Genet Cytogenet Oncol Haematol. 2010; 14(6):550-551.

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