Zbtb7

Last updated

Zbtb7, whose protein product is also known as Pokemon, is a gene that functions as a regulator of cellular growth and a proto oncogene.

Contents

Zbtb7 is a member of the POK (POZ and Krüppel) family of genes, [1] and the ZBTB protein family that contains zinc finger and BTB domains. [2] It is also known as LRF10 (leukemia/lymphoma-related factor), OCZF11 (osteoclast-derived zinc finger), [3] and FBI1 (1-3) (fourteen-three-three beta interactant). [4] [5] [6]

Zbtb7 is a transcription factor that regulates pathways involved in cell growth and transcription and it specifically represses many activities. [7] When this gene binds to a consensus sequence, it prevents transcription by controlling the conformation of chromatin and bringing other transcription factors to gene regulation sites. [7] This gene controls access to gene transcription regulation regions. [7] Zbtb7 prevents SP1, a transcription factor, from binding to DNA which will halt the process of transcribing DNA to RNA. [7] Downstream effects of Zbtb7 activity include failure to transcribe ARF, a critical tumor suppressor. [7] Zbtb7 is also involved in the regulation of p53, another tumor suppressor gene. [8] As an oncogene, Zbtb7 is overexpressed in many types of cancer, including lung, liver, prostate, and oral. [8]

Oncogenic studies on Zbtb7

In initial studies using mouse embryonic fibroblasts, researchers found that in the absence of Zbtb7, cellular pathways that convert normal cells into tumor cells did not develop. [9] However, when Zbtb7 was overexpressed, pathways for the transformation of normal cells to cancer cells resulted, both in vitro and in vivo . [9] From these observations, researchers concluded that Zbtb7 is often overexpressed in human cancers, and so it can be used to understand biological pathways and patient prognosis. [9]

The relationship between Zbtb7 and breast cancer has been investigated. [10] Based on a clinical study, it was concluded that the expression of Zbtb7 is related to the severity of the grade of cancer. [10] High expression of the gene was apparent in patients with grades II and III cancer, while low expression of the gene was found in patients with grade I and II tumors. [10] Zbtb7 can also serve as a biomarker for patient survival. [10] It was shown that patients with low expression of Zbtb7 were less likely to experience a recurrence in the following five years compared to those with high expression of the gene. [10]

Consistent results were concluded in a later study investigating the relationship between Zbtb7 expression and transitional cell carcinoma (TCC) in the bladder. [11] Higher expression of this gene was associated with later stage, more severe grade, higher recurrence, and lower survival. [11] As a result, it is assumed that Zbtb7 expression may be related to the onset, growth, and proliferation of TCC tumors. [11] Researchers stated that some of their data is not statistically significant due to a small sample size and failure to follow-up with patients, so further study is recommended to verify the relationship between Zbtb7 and TCC patient outcomes. [11]

Zbtb7 has also been studied in association with renal carcinoma. [12] The study indicated that Zbtb7 was present in abundance in renal carcinoma specimens and that overexpression of the gene was related to increases in cell growth and invasion into other cells and tissues. [12] However, when Zbtb7 was silenced, this activity was not apparent. miR-137, a tumor suppressor miRNA was found to decrease the expression of Zbtb7. [12] Interestingly, when Zbtb7 levels increase, it is capable of binding to the promoter region and preventing transcription of miR-137. [12] Together, Zbtb7 and miR-137 form an autoregulatory loop that mediates the onset, growth, and spread of cancer. [12]

Zbtb7 is abundantly expressed in colorectal cancer (CRC) as well. [8] Treatment for CRC includes administration of 5-Fluorouracil (5-FU), chemotherapy also used to treat other cancers, such as pancreatic cancer and breast cancer. [8] Some CRC patients have developed resistance to 5-FU. [8] It has been shown that overexpression of Zbtb7 may increase 5-FU resistance through the NF-[kappa]B signaling pathway and thus allow for further proliferation of cancer cells. [8] However, the introduction of SN50, an NF-[kappa]B inhibitor reverses resistance caused by Zbtb7. [8] Therefore, the relationship between Zbtb7 and NF-[kappa]B may be important in reducing 5-FU resistance in CRC patients. [8]

Etymology

Pokemon is the name given to the protein product of Zbtb7 gene by the research team at Memorial Sloan Kettering Cancer Center (MSKCC), which discovered its oncogenic function. It stands for "POKerythroid myeloid ontogenic[ sic ] [13] factor" and is most likely a backronym of the Pokémon media franchise. The Pokémon Company threatened MSKCC with legal action in December 2005 for creating an association between cancer and the media franchise, and as a consequence MSKCC is now referring to it by its gene name Zbtb7. [14]

Genes

See also

Related Research Articles

<span class="mw-page-title-main">T-box transcription factor T</span> Protein-coding gene in the species Homo sapiens

T-box transcription factor T, also known as Brachyury protein, is encoded for in humans by the TBXT gene. Brachyury functions as a transcription factor within the T-box family of genes. Brachyury homologs have been found in all bilaterian animals that have been screened, as well as the freshwater cnidarian Hydra.

<span class="mw-page-title-main">Protein inhibitor of activated STAT</span>

Protein inhibitor of activated STAT (PIAS), also known as E3 SUMO-protein ligase PIAS, is a protein that regulates transcription in mammals. PIAS proteins act as transcriptional co-regulators with at least 60 different proteins in order to either activate or repress transcription. The transcription factors STAT, NF-κB, p73, and p53 are among the many proteins that PIAS interacts with.

<span class="mw-page-title-main">CD24</span>

Signal transducer CD24 also known as cluster of differentiation 24 or heat stable antigen CD24 (HSA) is a protein that in humans is encoded by the CD24 gene. CD24 is a cell adhesion molecule.

<span class="mw-page-title-main">Alpha-enolase</span> Protein-coding gene in Homo sapiens

Enolase 1 (ENO1), more commonly known as alpha-enolase, is a glycolytic enzyme expressed in most tissues, one of the isozymes of enolase. Each isoenzyme is a homodimer composed of 2 alpha, 2 gamma, or 2 beta subunits, and functions as a glycolytic enzyme. Alpha-enolase, in addition, functions as a structural lens protein (tau-crystallin) in the monomeric form. Alternative splicing of this gene results in a shorter isoform that has been shown to bind to the c-myc promoter and function as a tumor suppressor. Several pseudogenes have been identified, including one on the long arm of chromosome 1. Alpha-enolase has also been identified as an autoantigen in Hashimoto encephalopathy.

<span class="mw-page-title-main">HMGA2</span> Protein-coding gene in the species Homo sapiens

High-mobility group AT-hook 2, also known as HMGA2, is a protein that, in humans, is encoded by the HMGA2 gene.

<span class="mw-page-title-main">BCL3</span> Protein-coding gene in the species Homo sapiens

B-cell lymphoma 3-encoded protein is a protein that in humans is encoded by the BCL3 gene.

<span class="mw-page-title-main">KLF4</span> Protein-coding gene in the species Homo sapiens

Kruppel-like factor 4 is a member of the KLF family of zinc finger transcription factors, which belongs to the relatively large family of SP1-like transcription factors. KLF4 is involved in the regulation of proliferation, differentiation, apoptosis and somatic cell reprogramming. Evidence also suggests that KLF4 is a tumor suppressor in certain cancers, including colorectal cancer. It has three C2H2-zinc fingers at its carboxyl terminus that are closely related to another KLF, KLF2. It has two nuclear localization sequences that signals it to localize to the nucleus. In embryonic stem cells (ESCs), KLF4 has been demonstrated to be a good indicator of stem-like capacity. It is suggested that the same is true in mesenchymal stem cells (MSCs).

<span class="mw-page-title-main">S100A2</span> Protein-coding gene in the species Homo sapiens

S100 calcium-binding protein A2 (S100A2) is a protein that in humans is encoded by the S100A2 gene and it is located on chromosome 1q21 with other S100 proteins.

<span class="mw-page-title-main">SNAI1</span> Protein

Zinc finger protein SNAI1 is a protein that in humans is encoded by the SNAI1 gene. Snail is a family of transcription factors that promote the repression of the adhesion molecule E-cadherin to regulate epithelial to mesenchymal transition (EMT) during embryonic development.

<span class="mw-page-title-main">ZEB1</span> Protein-coding gene in the species Homo sapiens

Zinc finger E-box-binding homeobox 1 is a protein that in humans is encoded by the ZEB1 gene.

<span class="mw-page-title-main">SALL4</span> Protein-coding gene in the species Homo sapiens

Sal-like protein 4(SALL4) is a transcription factor encoded by a member of the Spalt-like (SALL) gene family, SALL4. The SALL genes were identified based on their sequence homology to Spalt, which is a homeotic gene originally cloned in Drosophila melanogaster that is important for terminal trunk structure formation in embryogenesis and imaginal disc development in the larval stages. There are four human SALL proteins with structural homology and playing diverse roles in embryonic development, kidney function, and cancer. The SALL4 gene encodes at least three isoforms, termed A, B, and C, through alternative splicing, with the A and B forms being the most studied. SALL4 can alter gene expression changes through its interaction with many co-factors and epigenetic complexes. It is also known as a key embryonic stem cell (ESC) factor.

<span class="mw-page-title-main">ID4</span> Protein-coding gene in humans

ID4 is a protein coding gene. In humans, it encodes for the protein known as DNA-binding protein inhibitor ID-4. This protein is known to be involved in the regulation of many cellular processes during both prenatal development and tumorigenesis. This is inclusive of embryonic cellular growth, senescence, cellular differentiation, apoptosis, and as an oncogene in angiogenesis.

<span class="mw-page-title-main">MTA3</span> Protein-coding gene in the species Homo sapiens

Metastasis-associated protein MTA3 is a protein that in humans is encoded by the MTA3 gene. MTA3 protein localizes in the nucleus as well as in other cellular compartments MTA3 is a component of the nucleosome remodeling and deacetylate (NuRD) complex and participates in gene expression. The expression pattern of MTA3 is opposite to that of MTA1 and MTA2 during mammary gland tumorigenesis. However, MTA3 is also overexpressed in a variety of human cancers.

<span class="mw-page-title-main">LAPTM4B</span> Protein-coding gene in the species Homo sapiens

Lysosomal-associated transmembrane protein 4B is a protein that in humans is encoded by the LAPTM4B gene.

<span class="mw-page-title-main">EIF5A2</span> Protein-coding gene in the species Homo sapiens

Eukaryotic translation initiation factor 5A-2 is a protein that in humans is encoded by the EIF5A2 gene.

<span class="mw-page-title-main">ZNF703</span> Protein-coding gene in the species Homo sapiens

ZNF703 is a gene which has been linked with the development of breast cancers. ZNF703 is contained within the NET/N1z family responsible for regulation of transcription essential for developmental growth especially in the hindbrain. Normal functions performed by ZNF703 include adhesion, movement and proliferation of cells. ZNF703 directly accumulates histone deacetylases at gene promoter regions but does not bind to functional DNA.

<span class="mw-page-title-main">HOXA11-AS1</span> Long non-coding RNA from the antisense strand in the homeobox A (HOXA gene).

HOXA11-AS lncRNA is a long non-coding RNA from the antisense strand in the homeobox A. The HOX gene contains four clusters. The sense strand of the HOXA gene codes for proteins. Alternative names for HOXA11-AS lncRNA are: HOXA-AS5, HOXA11S, HOXA11-AS1, HOXA11AS, or NCRNA00076. This gene is 3,885 nucleotides long and resides at chromosome 7 (7p15.2) and is transcribed from an independent gene promoter. Being a lncRNA, it is longer than 200 nucleotides in length, in contrast to regular non-coding RNAs.

<span class="mw-page-title-main">MIR22HG</span> Non-coding RNA in the species Homo sapiens

MIR22HG, also known as C17orf91, MGC14376, MIRN22, hsa-mir-22, and miR-22 is a human gene that encodes a noncoding RNA (ncRNA).This RNA molecule is not translated into a protein but nonetheless may have important functions.

The nuclear protein in testis gene encodes a 1,132-amino acid protein termed NUT that is expressed almost exclusively in the testes, ovaries, and ciliary ganglion. NUT protein facilitates the acetylation of chromatin by histone acetyltransferase EP300 in testicular spermatids. This acetylation is a form of chromatin remodeling which compacts spermatid chromatin, a critical step required for the normal conduct of spermatogenesis, i.e. the maturation of spermatids into sperm. Male mice that lacked the mouse Nutm1 gene using a gene knockout method had abnormally small testes, lacked sperm in their cauda epididymis, and were completely sterile. These findings indicate that Nutm1 gene is essential for the development of normal fertility in male mice and suggest that the NUTM1 gene may play a similar role in men.

References

  1. ↑ Maeda, Takahiro; Hobbs, Robin M.; Pandolfi, Pier Paolo (2005). "The Transcription Factor Pokemon: A New Key Player in Cancer Pathogenesis". Cancer Research. 65 (19): 8575–8578. doi: 10.1158/0008-5472.CAN-05-1055 . PMID   16204018.
  2. ↑ Guo, Changcheng; Xiong, Dabo; Yang, Bin; Zhang, Haiming; Gu, Wenyu; Liu, Min; Yao, Xudong; Zheng, Junhua; Peng, Bo (October 2017). "The expression and clinical significance of ZBTB7 in transitional cell carcinoma of the bladder". Oncology Letters. 14 (4): 4857–4862. doi:10.3892/ol.2017.6814. PMC   5649710 . PMID   29085492.
  3. ↑ Kukita, A; Kukita, T; Ouchida, M; Maeda, H; Yatsuki, H; Kohashi, O (15 September 1999). "Osteoclast-derived zinc finger (OCZF) protein with POZ domain, a possible transcriptional repressor, is involved in osteoclastogenesis". Blood. 94 (6): 1987–97. doi:10.1182/blood.V94.6.1987. PMID   10477728.
  4. ↑ "FBI1 (Human)".
  5. ↑ Komiya, Yuko; Akiyama, Hirotada; Sakumoto, Ryuji; Tashiro, Fumio (February 2014). "FBI1/Akirin2 promotes tumorigenicity and metastasis of Lewis lung carcinoma cells". Biochemical and Biophysical Research Communications. 444 (3): 382–386. doi:10.1016/j.bbrc.2014.01.064. PMID   24468084.
  6. ↑ Jiang, Yuyang (23 March 2012). "Zbtb7 suppresses the expression of CDK2 and E2F4 in liver cancer cells: Implications for the role of Zbtb7 in cell cycle regulation". Molecular Medicine Reports. 5 (6): 1475–80. doi: 10.3892/mmr.2012.846 . PMID   22447046.
  7. 1 2 3 4 5 "ZBTB7A - Zinc finger and BTB domain-containing protein 7A - Homo sapiens (Human) - ZBTB7A gene & protein". www.uniprot.org. Retrieved 2021-04-25.
  8. 1 2 3 4 5 6 7 8 Wang, Zexin; Zhao, Xilan; Wang, Wei; Liu, Yishu; Li, Yanyan; Gao, Junyong; Wang, Cancan; Zhou, Meiyu; Liu, Ruyan; Xu, Guofa; Zhou, Qi (2018-08-10). "ZBTB7 evokes 5-fluorouracil resistance in colorectal cancer through the NF‑κB signaling pathway". International Journal of Oncology. 53 (5): 2102–2110. doi: 10.3892/ijo.2018.4521 . ISSN   1019-6439. PMID   30106136.
  9. 1 2 3 Maeda, Takahiro; Hobbs, Robin M.; Merghoub, Taha; Guernah, Ilhem; Zelent, Arthur; Cordon-Cardo, Carlos; Teruya-Feldstein, Julie; Pandolfi, Pier Paolo (January 2005). "Role of the proto-oncogene Pokemon in cellular transformation and ARF repression". Nature. 433 (7023): 278–285. Bibcode:2005Natur.433..278M. doi:10.1038/nature03203. PMID   15662416. S2CID   4308742.
  10. 1 2 3 4 5 Qu, Hongyan; Qu, Danni; Chen, Fuhui; Zhang, Zhenyu; Liu, Baogang; Liu, Haifeng (June 2010). "ZBTB7 Overexpression Contributes to Malignancy in Breast Cancer". Cancer Investigation. 28 (6): 672–678. doi:10.3109/07357901003631007. ISSN   0735-7907. PMID   20394500. S2CID   26171423.
  11. 1 2 3 4 Guo, Changcheng; Xiong, Dabo; Yang, Bin; Zhang, Haiming; Gu, Wenyu; Liu, Min; Yao, Xudong; Zheng, Junhua; Peng, Bo (October 2017). "The expression and clinical significance of ZBTB7 in transitional cell carcinoma of the bladder". Oncology Letters. 14 (4): 4857–4862. doi:10.3892/ol.2017.6814. ISSN   1792-1074. PMC   5649710 . PMID   29085492.
  12. 1 2 3 4 5 Wang, Lihui; Li, Qi; Ye, Zhuo; Qiao, Baoping (2019-09-23). "ZBTB7/miR-137 Autoregulatory Circuit Promotes the Progression of Renal Carcinoma". Oncology Research. 27 (9): 1007–1014. doi:10.3727/096504018X15231148037228. ISSN   0965-0407. PMC   7848413 . PMID   29673422.
  13. ↑ Spelled like this in the original article; likely a misspelling of oncogenic
  14. ↑ Brendan Sinclair (2005-12-19). "Pokémon USA threatens to sue cancer researchers". GameSpot . Retrieved 2016-01-31.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.