PEDF
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| Location (UCSC) | Chr 17: 1.76 – 1.78 Mb | Chr 11: 75.3 – 75.31 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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Pigment epithelium-derived factor (PEDF) also known as serpin F1 (SERPINF1), is a multifunctional secreted
Discovery
Pigment epithelium-derived factor (PEDF) was originally discovered by Joyce Tombran-Tink and Lincoln Johnson in the late 1980s.
Soon thereafter, the same laboratory
Gene
The
. The PEDF gene consists of 8 exons and 7 introns.The PEDF gene is present in vertebrates from human to fish, but not present in sea squirts, worms, or fruit flies.
Protein
The PEDF protein is a secreted protein of roughly 50kDa size and 418 amino acids in length.
In 2001, the crystal structure of PEDF was successfully generated.[15] The PEDF structure includes 3 beta sheets and 10 alpha helices. This discovery demonstrated that PEDF has an asymmetrical charge distribution across the whole protein. One side of the protein is heavily basic and the other side is heavily acidic, leading to a polar 3-D structure. They proposed that the basic side of the protein contains a heparin binding site.
Signaling
PEDF expression is upregulated by
Secreted PEDF binds a receptor on the cell surface termed
PEDF induces
Function
PEDF has a variety of functions including antiangiogenic, antitumorigenic, and neurotrophic properties.
The antitumorigenic effects of PEDF are not only due to inhibition of supporting vasculature, but also due to effects on the cancer cells themselves. PEDF was shown to inhibit cancer cell proliferation and increase apoptosis via the FAS/FASL pathway.[34] VEGF expression by cancer cells is inhibited by PEDF.[35]
PEDF also displays neurotrophic functions. Retinoblastoma cells differentiate into neurons due to the presence of PEDF.[9] Expression of PEDF in the human retina is found at 7.4 weeks of gestation, suggesting it may play a role in retinal neuron differentiation.[36]
Clinical significance
PEDF, a protein with many functions, has been suggested to play a clinical role in dry eye, choroidal neovascularization, cardiovascular disease, diabetes, diabetic macular edema, osteogenesis imperfecta and cancer.[37][26][28][30][38][39] As an antiangiogenic protein, PEDF may help suppress unwanted neovascularization of the eye. Molecules that shift the balance towards PEDF and away from VEGF may prove useful tools in both choroidal neovascularization and preventing cancer metastasis formation.[16][40][41]
References
- ^ a b c ENSG00000282307 GRCh38: Ensembl release 89: ENSG00000132386, ENSG00000282307 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000000753 – Ensembl, May 2017
- ^ "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.
- ^ S2CID 30871963.
- ^ "Entrez Gene: SERPINF1 serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 1".
- ^ PMID 8434014.
- PMID 2668219.
- ^ PMID 1936177.
- PMID 8188257.
- ^ PMID 17020603.
- PMID 15958558.
- PMID 8976566.
- PMID 7592790.
- PMID 11562499.
- ^ PMID 16735992.
- ^ PMID 11782462.
- PMID 16043845.
- PMID 16167083.
- PMID 17032652.
- ^ PMID 16339148.
- PMID 19224861.
- PMID 17651710.
- PMID 15044958.
- S2CID 3113843.
- ^ S2CID 12373314.
- PMID 10398599.
- ^ S2CID 22379964.
- PMID 11867604.
- ^ PMID 19850839.
- PMID 16919597.
- S2CID 9867297.
- PMID 16901919.
- PMID 15313901.
- PMID 15985268.
- PMID 11438800.
- PMID 32387568.
- PMID 16406543.
- PMID 21353196.
- PMID 16409998.
- PMID 15623988.