Zif268

Zif268

Zif268 is a mammalian transcription factor that is now officially known as Egr1 (Early Growth Response Protein 1). It was also named Krox-24, NGFI-A, TIS8, and ZENK. It was originally discovered in mouse.

PBB_Summary
section_title =
summary_text = The protein encoded by this gene belongs to the EGR family of C2H2-type zinc-finger proteins. It is a nuclear protein and functions as a transcriptional regulator. The products of target genes it activates are required for differentiation and mitogenesis. Studies suggest this is a tumor suppressor gene. [cite web | title = Entrez Gene: EGR1 early growth response 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1958| accessdate = ]

tructure

The DNA binding domain of Zif268 consists of three zinc finger domains of the Cys2His2 type.The amino acid structure of the Zif268 zinc finger domain is given in this table, using the single letter amino acid code. The fingers 1 to 3 are indicated by f1 - f3. The numbers are in reference to the residues (amino acids) of alpha helix (there is no '0'). The residues marked 'x' are not part of the zinc fingers, but rather serve to connect them all together.

The crystal structure of DNA bound by the zinc finger domain of Zif268 was solved in 1991, which greatly aided early research in zinc finger DNA-binding domains. [Pavletich, N. P. and C. O. Pabo (1991). "Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A." Science 252(5007): 809-17.]

The human Zif268/EGR1 protein contains (in its unprocessed form) 543 amino acids with a molecular weight of 57.5 kDa, and the gene is located on the chromosome 5.

Function

Zif268 binds the DNA sequence 5'-GCG [G/T] GGGCG-3'. [cite journal |author=Christy B, Nathans D |title=DNA binding site of the growth factor-inducible protein Zif268 |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=86 |issue=22 |pages=8737–41 |year=1989 |pmid=2510170 |doi= 10.1073/pnas.86.22.8737|url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=2510170] [cite journal |author=Swirnoff AH, Milbrandt J |title=DNA-binding specificity of NGFI-A and related zinc finger transcription factors |journal=Mol. Cell. Biol. |volume=15 |issue=4 |pages=2275–87 |year=1995 |pmid=7891721 |doi= |url=http://mcb.asm.org/cgi/pmidlookup?view=long&pmid=7891721]

It has a distinct pattern of expression in the brain, and its induction has been shown to be assiociated with neuronal activity. Several studies suggest it has a role in neuronal plasticity. [Knapska, E and Kaczmarek, L (2004) "A gene for Neuronal Plasticity in the Mammalian Brain: Zif286/Egr1/NGFI-A/Krox-24/TIS-8/ZENK?" Progress in Neurobiology 74, 2004]

Zif268 has also been found to regulate the expression of synaptobrevin II (a protein important for synaptic exocytosis). [Petersohn,D and Thiel. G (1996)"Role of zinc-finger proteins Sp1 and zif268/egr-1 in transcriptional regulation of the human synaptobrevin II gene" European Journal of Biochemistry, 239, 1996]

ee also

* Zinc finger

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=Heath RG |title=Brain function and behavior. I. Emotion and sensory phenomena in psychotic patients and in experimental animals |journal=J. Nerv. Ment. Dis. |volume=160 |issue= 3 |pages= 159–75 |year= 1975 |pmid= 1090709 |doi=
*cite journal | author=Silverman ES, Collins T |title=Pathways of Egr-1-mediated gene transcription in vascular biology |journal=Am. J. Pathol. |volume=154 |issue= 3 |pages= 665–70 |year= 1999 |pmid= 10079243 |doi=
*cite journal | author=Adamson ED, Mercola D |title=Egr1 transcription factor: multiple roles in prostate tumor cell growth and survival |journal=Tumour Biol. |volume=23 |issue= 2 |pages= 93–102 |year= 2002 |pmid= 12065847 |doi=10.1159/000059711
*cite journal | author=Blaschke F, Bruemmer D, Law RE |title=Egr-1 is a major vascular pathogenic transcription factor in atherosclerosis and restenosis |journal=Reviews in endocrine & metabolic disorders |volume=5 |issue= 3 |pages= 249–54 |year= 2004 |pmid= 15211096 |doi= 10.1023/B:REMD.0000032413.88756.ee
*cite journal | author=Abdulkadir SA |title=Mechanisms of prostate tumorigenesis: roles for transcription factors Nkx3.1 and Egr1 |journal=Ann. N. Y. Acad. Sci. |volume=1059 |issue= |pages= 33–40 |year= 2006 |pmid= 16382041 |doi= 10.1196/annals.1339.018

External links

*

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