Elongation factor 1-alpha 1 (eEF1a1) is a translation elongation
protein, expressed across eukaryotes. In humans, it is encoded by the EEF1A1gene.[5][6]
This gene encodes an
isoform of the alpha
subunit of the
elongation factor-1 complex, which is responsible for the enzymatic delivery of aminoacyl
tRNAs to the
ribosome. This isoform (alpha 1) is expressed in brain, placenta, lung, liver, kidney, and pancreas, and the other isoform (alpha 2) is expressed in brain, heart and skeletal muscle. This isoform is identified as an
autoantigen in 66% of patients with
Felty's syndrome. This gene has been found to have multiple copies on many
chromosomes, some of which, if not all, represent different
pseudogenes.[7]
Structure
Mammalian eEF1A possesses two
paralogs, eEF1A1 and
eEF1A2, with high amino acid sequence homology (approximately 90% identity).[8][9][10][11] The sequences of their
promoter regions are also highly similar, though that of the eEF1A2 gene contains an additional 81 bp SV40 small antigen sequence at the 5′-end.[12] The EEF1A15' UTR also contains a terminal oligo
pyrimidine tract.[13] Thus, these two isoforms demonstrate differences in expression and function: eEF1A1 is expressed in most cells while eEF1A2 is only expressed in adult neuronal and muscle cells, and only eEF1A1 induces
HSP70 during
heat shock.[11]
Function
The eEF1A1 protein is an isoform of the eEF-1 complex alpha subunit, an elongation factor protein, a
GTPase, and an
actin bundling protein.[7][8][9][14] As an elongation factor, it is known to mediate the recruitment of
aminoacyl-tRNA to the A-site of the 80S
ribosome during
protein synthesis.[8][14][15][16] As a result, this protein is ubiquitously expressed.[8][10][14]
In addition to its role in
translation, eEF1A has been shown to play a central role in the
nuclear export of proteins.[17][18][19] Thus, eEF1A can be found in both the
cytoplasm for translation and in the
nucleus for nuclear transport.[11]VHL,
PABP1 and other proteins containing a TD-NEM (Transcription Dependent Nuclear Export Motif) are exported by eEF1A in a manner that is dependent on ongoing
RNA polymerase II (RNA PolII)-dependent
transcription.[17]
Upregulation of eEF1A has been reported in
breast cancer samples.[20] Interestingly, however, this upregulation only occurs at the
protein level, because the
mRNA level is significantly reduced in
breast cancer samples.[20] This paradox has been explained by cell cycle-regulated EEF1A1 mRNA expression and stress-induced increase in eEF1A protein levels in breast cancer cells.[20][11] Though its role in
metastasis remains unclear, the role of eEF1A in cytoskeleton organization may promote tumor
cell motility and thus spread.[9] Alternatively, apoptotic cells may
secreteantigens, including eEF1A and other elongation factors, to induce an
autoimmune response during cancer. It is postulated that high expression and secretion of elongation factors from tumor tissues, combined with altered levels of eEF1A-derived bacterial peptides in
neoplastic disease, may lead to autoimmunity in breast cancer.[14]
As with breast cancer, upregulation of eEF1A expression is associated with
prostate cancer and worsened metastasis-free and overall patient survival.[9] Moreover, a truncated form of the eEF1A1 protein, prostate tumour inducing gene 1 (
PTI-1), has been detected in prostate carcinoma patient-derived blood samples. As eEF1A1 is over-expressed in
osteoblasts, which proliferate and
differentiate in the presence of tumor cells, it may serve as a
serumbiomarker to track the
metastatic progression of prostate cancer.[15]
In the case of acute
T lymphocytic leukemia, knocking down the eEF1A1 gene produces inhibited proliferation and induced apoptosis of
Jurkat cells. These effects may be attributed to the resulting down-regulation of the PI3K/Akt/NF-κB and PI3K/Akt/mTOR
signaling pathways.[21]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Lund A, Knudsen SM, Vissing H, Clark B, Tommerup N (Sep 1996). "Assignment of human elongation factor 1alpha genes: EEF1A maps to chromosome 6q14 and EEF1A2 to 20q13.3". Genomics. 36 (2): 359–61.
doi:
10.1006/geno.1996.0475.
PMID8812466.
^Wende H, Volz A, Ziegler A (Jul 2000). "Extensive gene duplications and a large inversion characterize the human leukocyte receptor cluster". Immunogenetics. 51 (8–9): 703–13.
doi:
10.1007/s002510000187.
PMID10941842.
S2CID20719684.
^
abcdefghijBecker M, Kuhse J, Kirsch J (Dec 2013). "Effects of two elongation factor 1A isoforms on the formation of gephyrin clusters at inhibitory synapses in hippocampal neurons". Histochemistry and Cell Biology. 140 (6): 603–9.
doi:
10.1007/s00418-013-1122-9.
PMID23839781.
S2CID12836593.
^
abcdefLiu H, Ding J, Chen F, Fan B, Gao N, Yang Z, Qi L (Nov 2010). "Increased expression of elongation factor-1α is significantly correlated with poor prognosis of human prostate cancer". Scandinavian Journal of Urology and Nephrology. 44 (5): 277–83.
doi:
10.3109/00365599.2010.492787.
PMID20545466.
S2CID13579193.
^Zhu J, Hayakawa A, Kakegawa T, Kaspar RL (Oct 2001). "Binding of the La autoantigen to the 5' untranslated region of a chimeric human translation elongation factor 1A reporter mRNA inhibits translation in vitro". Biochimica et Biophysica Acta. 1521 (1–3): 19–29.
doi:
10.1016/s0167-4781(01)00277-9.
PMID11690632.
^
abcdefghHamrita B, Nasr HB, Hammann P, Kuhn L, Guillier CL, Chaieb A, Khairi H, Chahed K (Sep 2011). "An elongation factor-like protein (EF-Tu) elicits a humoral response in infiltrating ductal breast carcinomas: an immunoproteomics investigation". Clinical Biochemistry. 44 (13): 1097–104.
doi:
10.1016/j.clinbiochem.2011.06.005.
PMID21704614.
^Huang Y, Hu JD, Qi YL, Wu YA, Zheng J, Chen YY, Huang XL (Aug 2012). "[Effect of knocking down eEF1A1 gene on proliferation and apoptosis in Jurkat cells and its mechanisms]". Zhongguo Shi Yan Xue Ye Xue Za Zhi. 20 (4): 835–41.
PMID22931638.
Brands JH, Maassen JA, van Hemert FJ, Amons R, Möller W (Feb 1986). "The primary structure of the alpha subunit of human elongation factor 1. Structural aspects of guanine-nucleotide-binding sites". European Journal of Biochemistry. 155 (1): 167–71.
doi:
10.1111/j.1432-1033.1986.tb09472.x.
PMID3512269.
Opdenakker G, Cabeza-Arvelaiz Y, Fiten P, Dijkmans R, Van Damme J, Volckaert G, Billiau A, Van Elsen A, Van der Schueren B, Van den Berghe H (Apr 1987). "Human elongation factor 1 alpha: a polymorphic and conserved multigene family with multiple chromosomal localizations". Human Genetics. 75 (4): 339–44.
doi:
10.1007/BF00284104.
PMID3570288.
S2CID19189698.
Carvalho MD, Carvalho JF, Merrick WC (Nov 1984). "Biological characterization of various forms of elongation factor 1 from rabbit reticulocytes". Archives of Biochemistry and Biophysics. 234 (2): 603–11.
doi:
10.1016/0003-9861(84)90310-2.
PMID6568109.
Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4.
doi:
10.1016/0378-1119(94)90802-8.
PMID8125298.
Sanders J, Brandsma M, Janssen GM, Dijk J, Möller W (May 1996). "Immunofluorescence studies of human fibroblasts demonstrate the presence of the complex of elongation factor-1 beta gamma delta in the endoplasmic reticulum". Journal of Cell Science. 109 (5): 1113–7.
doi:
10.1242/jcs.109.5.1113.
hdl:
1854/LU-01GJAXGWEXX2G4TPB1AKB720BQ.
PMID8743958.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56.
doi:
10.1016/S0378-1119(97)00411-3.
PMID9373149.