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| Version | Summary | Created by | Modification | Content Size | Created at | Operation |
|---|---|---|---|---|---|---|
| 1 | Vivi Li | + 314 word(s) | 314 | 2020-12-15 07:53:15 |
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FIP1 like 1 (S. cerevisiae)
1. Normal Function
The FIP1L1 gene provides instructions for making part of a protein complex named cleavage and polyadenylation specificity factor (CPSF). This complex of proteins plays an important role in processing molecules called messenger RNAs (mRNAs), which serve as the genetic blueprints for making proteins. The CPSF protein complex helps add a string of the RNA building block adenine to the mRNA, creating a polyadenine tail or poly(A) tail. The poly(A) tail is important for stability of the mRNA and for protein production from the blueprint.
2. Health Conditions Related to Genetic Changes
2.1 PDGFRA-Associated Chronic Eosinophilic Leukemia
A deletion of genetic material from chromosome 4 brings together part of the FIP1L1 gene and part of another gene called PDGFRA, creating the FIP1L1-PDGFRA fusion gene. This mutation is a somatic mutation, which means it is acquired during a person's lifetime and is present only in certain cells. This fusion gene causes PDGFRA-associated chronic eosinophilic leukemia, which is a type of blood cell cancer characterized by an increased number of eosinophils, a type of white blood cell involved in allergic reactions.
The FIP1L1-PDGFRA protein produced from the fusion gene has the function of the normal PDGFRA protein, which stimulates signaling pathways inside the cell that control many important cellular processes, such as cell growth and division (proliferation) and cell survival. Unlike the normal PDGFRA protein, however, the FIP1L1-PDGFRA protein is constantly turned on (constitutively activated), which means the cells are always receiving signals to proliferate. When the FIP1L1-PDGFRA fusion gene occurs in blood cell precursors, the growth of eosinophils (and occasionally other blood cells) is poorly controlled, leading to PDGFRA-associated chronic eosinophilic leukemia. It is unclear why eosinophils are preferentially affected by this genetic change.
3. Other Names for This Gene
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FIP1-like 1 protein
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FIP1_HUMAN
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hFip1
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pre-mRNA 3'-end-processing factor FIP1
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Rhe
References
- Bain BJ. Relationship between idiopathic hypereosinophilic syndrome,eosinophilic leukemia, and systemic mastocytosis. Am J Hematol. 2004Sep;77(1):82-5. Review.
- Buitenhuis M, Verhagen LP, Cools J, Coffer PJ. Molecular mechanisms underlyingFIP1L1-PDGFRA-mediated myeloproliferation. Cancer Res. 2007 Apr 15;67(8):3759-66.
- Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, Cortes J, Kutok J, ClarkJ, Galinsky I, Griffin JD, Cross NC, Tefferi A, Malone J, Alam R, Schrier SL,Schmid J, Rose M, Vandenberghe P, Verhoef G, Boogaerts M, Wlodarska I, KantarjianH, Marynen P, Coutre SE, Stone R, Gilliland DG. A tyrosine kinase created byfusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib inidiopathic hypereosinophilic syndrome. N Engl J Med. 2003 Mar 27;348(13):1201-14.
- Fukushima K, Matsumura I, Ezoe S, Tokunaga M, Yasumi M, Satoh Y, Shibayama H, Tanaka H, Iwama A, Kanakura Y. FIP1L1-PDGFRalpha imposes eosinophil lineagecommitment on hematopoietic stem/progenitor cells. J Biol Chem. 2009 Mar20;284(12):7719-32. doi: 10.1074/jbc.M807489200.
- Kaufmann I, Martin G, Friedlein A, Langen H, Keller W. Human Fip1 is a subunitof CPSF that binds to U-rich RNA elements and stimulates poly(A) polymerase. EMBOJ. 2004 Feb 11;23(3):616-26.
- Roufosse FE, Goldman M, Cogan E. Hypereosinophilic syndromes. Orphanet J Rare Dis. 2007 Sep 11;2:37. Review.
