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Fez1

Official Full Name
fasciculation and elongation protein zeta 1 (zygin I)
Background
Fasciculation and elongation protein zeta-1 is a protein that in humans is encoded by the FEZ1 gene.This gene is an ortholog of the C. elegans unc-76 gene, which is necessary for normal axonal bundling and elongation within axon bundles. Expression of this gene in C. elegans unc-76 mutants can restore to the mutants partial locomotion and axonal fasciculation, suggesting that it also functions in axonal outgrowth. The N-terminal half of the gene product is highly acidic. Alternatively spliced transcript variants encoding different isoforms of this protein have been described.
Synonyms
Fasciculation and elongation protein zeta 1; Fasciculation and elongation protein zeta-1; Fez 1; Fez; Fez-like zinc finger protein; FEZ1; Fezl; Forebrain embryonic zinc-finger like protein; Zpf312; Zygin 1; Zygin-1; ZyginI; fasciculation and elongation protein zeta 1 (zygin I); zygin I; zgc:73258; wu:fj14c12

The FEZ1 gene is located on chromosome 8p22, and it encodes a leucine zipper protein with a relative molecular mass of 67 × 103, which has a growth regulation effect. FEZ1 gene plays a very important role in the occurrence and development of many human malignant tumors, including prostate cancer, gastric cancer, head and neck cancer, bladder cancer, hepatocellular carcinoma, cholangiocarcinoma, and hematological malignancies.

FEZ proteins cytoplasmic function as transport bivalent adaptors.Figure 1. FEZ proteins cytoplasmic function as transport bivalent adaptors. (Teixeira, M., et al. 2019)

FEZ1 Expression in the Organization

In lung cancer, the researchers used immunohistochemical methods to analyze 103 cases of primary lung cancer (including 98 cases of non-small cell lung cancer, 57 cases of adenocarcinoma, 32 cases of squamous cell carcinoma, 7 cases of large cell carcinoma, and 2 cases). The expression of FEZ1 gene in 5 cases of other tissue types) and 5 cases of small cell carcinoma. The results showed that 27 cases had FEZ1 gene deletion, and 43 cases had significantly reduced expression. In addition, the results showed that the FEZ1 gene was positively correlated with tumor grade. Therefore, it is believed that FEZ1 gene plays an important role in lung cancer, and it is speculated that it may be used as a new prognostic indicator of lung cancer.

In bladder cancer, researchers used Western blot and immunohistochemistry methods to study the expression of FEZ1 protein in bladder transitional cell carcinoma-derived cell lines and primary bladder cancer. Among the bladder transitional cell carcinoma-derived cell lines, FEZ1 protein was missing or down-regulated in 4/5 cell lines, and FEZ1 protein was missing or down-regulated in 37 of 60 primary cancers. Another 37% of primary transitional cell carcinoma of the bladder and 70% of bladder transitional cell carcinoma-derived cell lines showed a significant decrease in FEZ1 protein expression. At the same time, statistical analysis showed that the down-regulation and lack of FEZ1 expression are significantly correlated with the grade of bladder cancer. In addition, studies have shown that the mRNA level and transcription products of FEZ1 gene are significantly reduced in most bladder transitional cell carcinoma-derived cell lines and primary bladder cancer, and it is believed that the mechanism of FEZ1 gene inactivation may be the promoter hypermethylation.

FEZ1 Inhibits Tumor Cell Growth

Using gastric cancer carcinogen NMBA to induce tumors in mice lacking endogenous FEZ1 gene to study the role of FEZ1 in living tumors. The results of the study showed that after 6 weeks of administration, FEZ1 (-/-) mice (20/20) and FEZ1 (+/-) mice had complex tumor growth in the cardiac sinus, while only (5/19) Wild-type mice have the potential to develop tumors. In addition, only the first two types of mice have invasive growth tumors, and wild-type mice show a series of injuries including hyperplasia and papilloma.

It was observed that untreated mice lacking the FEZ1 gene had spontaneous tumors after 2 years. 5 FEZ1 (-/-) and FEZ1 (+/-) mice had new tumor growth, while 3 wild-type mice No new tumors were found in the mice. Observing spontaneous tumors and induced tumors in mice with inactivated FEZ1 alleles, researchers infer that FEZ1 can inhibit the growth of tumor cells. In addition, when researchers studied bladder cancer cell lines lacking the endogenous FEZ1 gene, they were transduced to restore expression in vitro, and they also observed the inhibitory effect of FEZ1 on tumor cell growth. This effect is related to FEZ1's ability to regulate cell mitosis.

References:

  1. Teixeira, M., Alborghetti, M. R., & Kobarg, J. (2019). Fasciculation and elongation zeta proteins 1 and 2: From structural flexibility to functional diversity. World Journal of Biological Chemistry, 10(2), 28-43.
  2. Huang, P., Summers, B. J., Xu, C., Perilla, J. R., Malikov, V., Naghavi, M. H., & Xiong, Y. (2019). FEZ1 Is Recruited to a Conserved Cofactor Site on Capsid to Promote HIV-1 Trafficking. Cell Reports, 28(9).
  3. Chen, X., Ku, L., Mei, R., Liu, G., Xu, C., Wen, Z., Zhao, X., Wang, F., Xiao, L., & Feng, Y. (2017). Novel schizophrenia risk factor pathways regulate FEZ1 to advance oligodendroglia development. Translational psychiatry, 7(12), 1293.

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