Affinage

FIP1L1

Pre-mRNA 3'-end-processing factor FIP1 · UniProt Q6UN15

Length
594 aa
Mass
66.5 kDa
Annotated
2026-04-28
100 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FIP1L1 encodes hFip1, an intrinsically disordered scaffold subunit of the cleavage and polyadenylation specificity factor (CPSF) complex that is essential for mRNA 3'-end processing and alternative polyadenylation (APA). Two copies of hFip1 bind CPSF30 zinc fingers ZF4 and ZF5 to recruit poly(A) polymerase (PAP) via its arginine-rich RNA-binding motif that preferentially recognizes U-rich elements, while CstF77 competitively inhibits PAP recruitment through a distinct hFip1 N-terminal interaction, providing a regulatory switch for polyadenylation (PMID:14749727, PMID:33122294, PMID:36073787). hFip1-directed APA is required for embryonic stem cell self-renewal and somatic cell reprogramming, and regulates inflammatory gene expression through 3'UTR shortening of targets such as NLRP3 (PMID:24596251, PMID:34011928). A cryptic interstitial deletion on chromosome 4q12 fuses FIP1L1 to PDGFRα, generating a constitutively active tyrosine kinase—driven by loss of the PDGFRα juxtamembrane autoinhibitory domain rather than by the FIP1L1 moiety—that activates STAT5, PI3K/Akt, ERK, p38, JAK2, NF-κB, and SHP2 pathways to cause imatinib-sensitive myeloproliferative neoplasm with eosinophilia (PMID:12660384, PMID:16690743, PMID:17440089, PMID:24618081).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1995 High

    The founding discovery that yeast Fip1 is an essential polyadenylation factor that directly tethers poly(A) polymerase to the cleavage machinery established FIP1 as a core 3'-end processing component, resolving how PAP is recruited to pre-mRNA substrates.

    Evidence Two-hybrid, reconstitution of 1:1 Fip1–Pap1 complex, in vitro processing assay with thermosensitive allele in S. cerevisiae

    PMID:7736590

    Open questions at the time
    • Human ortholog not yet characterized
    • RNA-binding specificity of Fip1 unknown
    • Structural basis of Fip1–Pap1 interaction unresolved
  2. 2001 High

    Domain mapping of yeast Fip1 revealed a dual-function architecture: one region binds and inhibits Pap1 while another contacts Yth1 (CPSF30 ortholog), explaining how Fip1 both represses nonspecific polyadenylation and enables site-specific poly(A) addition.

    Evidence Deletion mutagenesis with in vitro polyadenylation and binding assays in yeast

    PMID:11238938

    Open questions at the time
    • How Fip1-mediated repression is relieved in the full complex unknown
    • No structural data on Fip1–Yth1 interface
  3. 2003 High

    Identification of the FIP1L1-PDGFRα fusion as a constitutively activated kinase caused by a 4q12 interstitial deletion established the molecular basis of imatinib-responsive hypereosinophilic syndrome, and the T674I gatekeeper mutation explained clinical imatinib resistance.

    Evidence Cell transformation assays, kinase inhibition (IC50 3.2 nM), sequencing of relapsed patient; confirmed in murine BM transplant model with PKC412 rescue

    PMID:12660384 PMID:12781364

    Open questions at the time
    • Which portion of the fusion drives activation unclear
    • Downstream effector pathways not mapped
    • Mechanism of eosinophil lineage specificity unknown
  4. 2004 High

    Biochemical characterization of human hFip1 demonstrated it is a CPSF subunit with an arginine-rich motif that binds U-rich RNA and stimulates PAP activity, establishing conservation of the yeast Fip1 mechanism in mammals.

    Evidence Recombinant protein reconstitution, in vitro polyadenylation, co-IP, RNA-binding assay

    PMID:14749727

    Open questions at the time
    • Stoichiometry of hFip1 within CPSF unknown
    • Structural basis of hFip1–CPSF30 interaction unresolved
  5. 2006 High

    Mutagenesis of FIP1L1-PDGFRα demonstrated that constitutive kinase activation requires disruption of the PDGFRα juxtamembrane autoinhibitory domain, while the FIP1L1 moiety is entirely dispensable, resolving a key question about the activation mechanism.

    Evidence Deletion mutagenesis, in vitro kinase assays, Ba/F3 transformation, murine models

    PMID:16690743

    Open questions at the time
    • Role of FIP1L1 portion in signaling specificity or protein stability not addressed
    • Mechanism of eosinophil commitment still unknown
  6. 2007 High

    Mapping of FIP1L1-PDGFRα downstream signaling in human CD34+ progenitors revealed that STAT5 and Akt activation require the FIP1L1 N-terminal portion (aa 30–233) while ERK and p38 do not, showing the fusion partners differentially route oncogenic signals.

    Evidence Retroviral transduction of human CD34+ cells, dominant-negative STAT5, PI3K/ERK inhibitors, colony assays

    PMID:17440089

    Open questions at the time
    • Molecular basis of FIP1L1 requirement for STAT5/Akt signaling unclear
    • In vivo validation in patient-derived cells limited
  7. 2008 High

    Crystal structure of the yeast Fip1 peptide–Pap1 complex revealed that Fip1 is intrinsically disordered and binds the outer surface of Pap1's C-terminal domain, providing the first atomic view of how this scaffold restricts polymerase activity.

    Evidence X-ray crystallography (2.6 Å), analytical ultracentrifugation, CD, lethal Pap1 mutants

    PMID:18537269

    Open questions at the time
    • Full-length Fip1 structure unavailable
    • Human hFip1–PAP complex structure unresolved
  8. 2009 High

    Two studies established that FIP1L1-PDGFRα escapes Cbl-mediated ubiquitination (explaining its stability compared to wild-type receptors) and imposes eosinophil lineage commitment through MEK1/2–p38–C/EBPα/GATA signaling, connecting protein turnover and lineage specification to disease phenotype.

    Evidence Pulse-chase stability assays, ubiquitination assays, destabilizing domain fusions; murine progenitor transduction with kinase inhibitors and shRNA, BM transplantation

    PMID:19147501 PMID:19644140

    Open questions at the time
    • How fusion evades Cbl ubiquitination structurally is unknown
    • Whether lineage commitment mechanism operates identically in human patients unclear
  9. 2014 High

    hFip1 was shown to be essential for embryonic stem cell self-renewal through regulation of ESC-specific alternative polyadenylation programs, establishing FIP1L1 as a master regulator of APA in cell fate decisions beyond constitutive 3'-end processing.

    Evidence Fip1 knockout/knockdown in mouse ESCs, RNA-seq/APA profiling, reprogramming assays

    PMID:24596251

    Open questions at the time
    • Mechanism by which Fip1 selects specific APA sites over others not resolved
    • Whether hFip1 levels regulate APA in adult somatic tissues unknown
  10. 2014 High

    Identification of SHP2 binding to phospho-Y720 of FIP1L1-PDGFRα as required for ERK signaling and transformation but dispensable for STAT5 activation revealed a branchpoint separating two major oncogenic pathways downstream of the fusion.

    Evidence Y720 mutagenesis, direct binding assay, SHP2 knockdown, murine BM transplantation, human CD34+ assays

    PMID:24618081

    Open questions at the time
    • Other phosphotyrosine docking sites on the fusion not systematically mapped
    • Whether SHP2 inhibitors have therapeutic utility not tested
  11. 2020 High

    Crystal structures of hFip1 bound to CPSF30 ZF4 and ZF5 revealed that CPSF contains two copies of hFip1, each recruiting one PAP molecule, establishing the stoichiometric and structural basis for multivalent PAP recruitment within the mammalian polyadenylation machinery.

    Evidence X-ray crystallography (1.9 Å), fluorescence polarization binding (Kd 1.8 nM for ZF4), mutagenesis, in vitro polyadenylation

    PMID:33122294

    Open questions at the time
    • Functional consequence of having two PAP copies versus one not determined
    • Full CPSF holoenzyme structure with hFip1 not available
  12. 2022 High

    Discovery that CstF77 binds hFip1's N-terminal region and competitively inhibits PAP recruitment revealed a built-in regulatory switch within CPSF that controls the transition from cleavage to polyadenylation.

    Evidence Crystal structures of hFip1–CstF77 complex, in vitro polyadenylation assays showing competitive inhibition

    PMID:36073787

    Open questions at the time
    • How CstF77 release is triggered during the cleavage-to-polyadenylation transition in vivo unknown
    • Regulation of this switch in APA site selection not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of hFip1's RNA-binding specificity for U-rich elements, the mechanism by which hFip1 selects between proximal and distal polyadenylation sites in vivo, and whether the two copies of hFip1 within CPSF serve functionally distinct roles remain unresolved.
  • No structure of hFip1 arginine-rich domain bound to RNA
  • No genome-wide dissection of individual hFip1 copy contributions
  • How hFip1-driven APA interfaces with transcription elongation rate is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-8953854 Metabolism of RNA 7 R-HSA-1643685 Disease 6 R-HSA-162582 Signal Transduction 4 R-HSA-74160 Gene expression (Transcription) 2
Partners
CBLCPSF1CPSF4CSTF3PAPOLAPDGFRASHP2
Complex memberships
CPSF (cleavage and polyadenylation specificity factor)

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 FIP1L1-PDGFRA fusion is a constitutively activated tyrosine kinase generated by an interstitial deletion on chromosome 4q12, which transforms hematopoietic cells; imatinib inhibits this kinase with an IC50 of 3.2 nM, and a T674I resistance mutation in the PDGFRA kinase domain confers imatinib resistance. Cell transformation assay, kinase inhibition assay, sequencing of resistance mutation in relapsed patient The New England journal of medicine High 12660384
2003 The T674I mutation in FIP1L1-PDGFRalpha (analogous to T315I in BCR-ABL) confers imatinib resistance, and PKC412 can overcome this resistance both in vitro and in a murine bone marrow transplant model of FIP1L1-PDGFRalpha-induced myeloproliferative disease. Murine bone marrow transplant model, in vitro kinase inhibition, cell proliferation assays Cancer cell High 12781364
2006 Constitutive activation of FIP1L1-PDGFRalpha requires disruption of the juxtamembrane (JM) domain of PDGFRalpha between two conserved tryptophan residues; the FIP1L1 portion is completely dispensable for kinase activation, and the presence of an intact JM domain is autoinhibitory (overcomeable by enforced homodimerization). Deletion mutagenesis, in vitro kinase activity assays, in vivo transformation assays in Ba/F3 cells and murine models Proceedings of the National Academy of Sciences of the United States of America High 16690743
2004 Human Fip1 (hFip1) is an integral subunit of CPSF; it interacts with poly(A) polymerase (PAP) and has an arginine-rich RNA-binding motif that preferentially binds U-rich sequence elements on pre-mRNA; recombinant hFip1 is sufficient to stimulate PAP polyadenylation activity in a U-rich element-dependent manner; hFip1, CPSF160, and PAP form a ternary complex in vitro. Recombinant protein reconstitution, in vitro polyadenylation assay, co-immunoprecipitation, RNA-binding assay The EMBO journal High 14749727
1995 Yeast Fip1 (ortholog of human FIP1L1) directly interacts with poly(A) polymerase (Pap1) in a 1:1 complex; it is an essential component of polyadenylation factor I (PF I); Fip1 tethers Pap1 to cleavage factor I (CF I) via direct interaction with RNA14; loss of Fip1 specifically abolishes polyadenylation (but not cleavage) in vitro. Two-hybrid assay, in vitro reconstitution (1:1 complex with Pap1), in vitro 3'-end processing assay with thermosensitive allele, co-immunoprecipitation Cell High 7736590
2001 Yeast Fip1 has distinct functional domains: amino acids 80-105 bind Pap1 and inhibit its activity (by restricting RNA access to Pap1's C-terminal RNA-binding domain); amino acids 206-220 interact with Yth1 and are required for specific polyadenylation; the C-terminus of Fip1 is required to relieve Fip1-mediated repression of Pap1. Domain deletion mutagenesis, in vitro polyadenylation assay, binding assays Molecular and cellular biology High 11238938
2008 Crystal structure of yeast poly(A) polymerase in complex with Fip1 peptide (residues 80-105) at 2.6 Å resolution shows the Fip1 peptide binding to the outside surface of the C-terminal domain of Pap1; Fip1 is largely intrinsically disordered in solution; a lethal polymerase mutant (V498Y, C485R) that cannot bind Fip1 but retains full polymerase activity was engineered. X-ray crystallography, analytical ultracentrifugation, circular dichroism, mutagenesis Biochemistry High 18537269
2011 Yeast Fip1 contains a flexible linker region in the middle of the protein; removal or replacement of this linker impairs polyadenylation efficiency; the linker provides a platform for critical interactions with other processing machinery components, and direct tethering of Pap1 to RNA rescues polyadenylation. In vitro polyadenylation assay, fusion protein complementation in vivo, genetic assays in yeast RNA (New York, N.Y.) High 21282348
2014 Mouse Fip1 is essential for embryonic stem cell (ESC) self-renewal and somatic cell reprogramming; Fip1 promotes stem cell maintenance by activating ESC-specific alternative polyadenylation (APA) profiles through Fip1-RNA interactions and proximity between APA sites; Fip1 expression and the APA program change during ESC differentiation and are restored during reprogramming. Genetic loss-of-function (Fip1 knockout/knockdown), RNA-seq/APA profiling, reprogramming assays The EMBO journal High 24596251
2020 Crystal structure of human CPSF30 ZF4-ZF5 in complex with hFip1 residues 161-200 at 1.9 Å resolution shows one hFip1 molecule binding each of ZF4 and ZF5 with a conserved interaction mode; CPSF contains two copies of hFip1; ZF4 has higher affinity (Kd = 1.8 nM); two copies of PAP are recruited by the CPSF30-hFip1 complex, both supporting polyadenylation. X-ray crystallography, mutagenesis, fluorescence polarization binding assay, in vitro polyadenylation assay Genes & development High 33122294
2021 Yeast Fip1 anchors poly(A) polymerase Pap1 onto the CPF complex via interaction with zinc finger 4 of Yth1 (CPSF30 ortholog); NMR spectroscopy of selectively labeled Fip1 in a reconstituted 850-kDa CPF complex shows that the Fip1 IDR connecting Yth1- and Pap1-binding sites remains highly dynamic within the complex. Reconstitution of fully recombinant CPF, NMR spectroscopy, binding assays Genes & development High 34593603
2022 Human Fip1 (hFip1) acts as a multivalent scaffold within CPSF: two copies of hFip1 each bind to ZF4 and ZF5 of CPSF30 (independently redundant for PAP recruitment); hFip1 interacts with CstF77 via a short motif in its N-terminal acidic region; CstF77 competitively inhibits CPSF-dependent PAP recruitment and polyadenylation. Crystal structures of hFip1-CPSF30 and hFip1-CstF77 complexes, in vitro polyadenylation assays eLife High 36073787
2007 FIP1L1-PDGFRalpha activates multiple downstream signaling pathways in human hematopoietic progenitors: STAT5 and Akt activation require the FIP1L1 portion (aa 30-233), whereas p38 and ERK1/2 are activated by both full-length and truncated FIP1L1-PDGFRalpha; combined inhibition of PI3K and ERK1/2 significantly reverses FIP1L1-PDGFRalpha-induced colony formation; dominant-negative STAT5 partially inhibits colony formation. Retroviral transduction of human CD34+ progenitors, dominant-negative constructs, small-molecule pathway inhibitors, colony assays Cancer research High 17440089
2009 FIP1L1-PDGFRalpha imposes eosinophil lineage commitment on hematopoietic stem/progenitor cells by more intensely activating MEK1/2 and p38 MAPK than TEL-PDGFRbeta; MEK1/2 and p38 inhibitors suppress this eosinophil development; FIP1L1-PDGFRalpha augments C/EBPalpha, GATA-1, and GATA-2 expression and suppresses PU.1 transcriptional activity via Ras. Murine hematopoietic progenitor transduction, kinase inhibitors, shRNA knockdown, luciferase reporter assays, bone marrow transplantation The Journal of biological chemistry High 19147501
2009 FIP1L1-PDGFRalpha and TEL-PDGFRbeta fusion proteins escape ubiquitination and proteasomal degradation (unlike wild-type activated receptors); Cbl-mediated ubiquitination is strongly reduced for the fusion proteins despite Cbl being phosphorylated; reducing SRC activity stabilizes FIP1L1-PDGFRalpha, and forced destabilization of the fusion reduces STAT5 activation and cell transformation. Pulse-chase protein stability assays, ubiquitination assays, destabilizing domain fusion constructs, patient leukocyte analysis Haematologica High 19644140
2012 FIP1L1-PDGFRalpha activates JAK2, which is required for fusion kinase-induced proliferation and migration; JAK2 inhibition reduces STAT3 activation (not STAT5), and also reduces PI3K/Akt and NF-κB activity; JAK2 mediates IL-5-induced migration of FIP1L1-PDGFRalpha-positive cells. siRNA knockdown, JAK2 inhibitor AG490, signaling pathway analysis (Western blot) in EOL-1 and primary patient cells PloS one Medium 22523564
2012 FIP1L1-PDGFRalpha activates NF-κB via PI3K; NF-κB activity is required for eosinophil differentiation marker expression (IL-5 receptor, eosinophil peroxidase) and colony formation from transduced human CD34+ hematopoietic progenitors; bortezomib and IκB kinase inhibitor block EOL-1 cell proliferation. Lentiviral transduction of human CD34+ cells, PI3K inhibitor, dominant-negative IκB, bortezomib treatment, expression microarrays Haematologica Medium 22271894
2014 SHP2 phosphatase binds directly to phospho-tyrosine 720 of FIP1L1-PDGFRalpha; this interaction is required for ERK signaling and cell transformation but not for STAT5 phosphorylation; mutation of Y720 inhibits myeloproliferation in transplanted mice and human CD34+ progenitor proliferation. Tyrosine mutagenesis, direct binding assay, SHP2 knockdown, in vivo murine bone marrow transplantation, human CD34+ progenitor assays Molecular oncology High 24618081
2015 The F604S mutation in FIP1L1-PDGFRalpha creates a binding site for the phosphatase domain of SHP-2, reducing CBL activation and SRC-dependent destabilization, thereby strongly stabilizing the fusion protein; SRC inhibition/knockdown mimics the stabilizing effect, establishing SRC as a regulator of FIP1L1-PDGFRalpha protein stability. Pulse-chase protein stability assay, SHP-2 binding assay, SRC inhibition/knockdown, mutagenesis screen Leukemia Medium 25761934
2014 The FIP1 motif in FIP1L1-RARA plays a pivotal role in homodimerization and transcriptional repressor activity of the fusion; in FIP1L1-PDGFRalpha, the C-terminal PDGFRalpha portion alone can homodimerize and constitutively activate the kinase, making FIP1L1 dispensable for kinase activation but contributing to full IL-3 independence. Deletion mutant analysis, hematopoietic cell transformation assays in BAF-B03 cells Annals of hematology Medium 24763514
2006 FIP1L1-PDGFRalpha cooperates with IL-5 to induce HES/CEL-like disease in mice; transplantation of FIP1L1-PDGFRalpha-positive HSCs alone produces a CML-like phenotype, but combined with IL-5 transgenic overexpression produces intense eosinophilia and multi-organ eosinophil infiltration, demonstrating that FIP1L1-PDGFRalpha is not sufficient alone and requires a second cytokine-driven event. Bone marrow transplantation in mice with IL-5 transgenic background; secondary transplantation Blood High 16418325
2008 FIP1L1/PDGFRalpha synergizes with SCF/c-kit signaling to promote mast cell development; SCF stimulates greater migration and Akt activation in FIP1L1/PDGFRalpha-expressing mast cells, and anti-c-kit antibody reduces but does not abolish F/P-induced intestinal mast cell infiltration in vivo. Murine bone marrow transplantation, anti-c-kit antibody neutralization, in vitro mast cell cytokine-independent proliferation and migration assays, Akt signaling analysis Blood Medium 18539901
2006 Sorafenib is a potent inhibitor of FIP1L1-PDGFRalpha and the imatinib-resistant T674I mutant, inducing apoptosis of EOL-1 cells at low nanomolar concentrations and blocking FIP1L1-PDGFRalpha phosphorylation by Western blot. Cell proliferation assay (Ba/F3 transformed cells, EOL-1), Western blot for kinase phosphorylation, apoptosis assay Blood High 16645167
2007 FIP1L1-PDGFRalpha induces eosinophil cell proliferation through induction of c-Myc expression via ERK and JNK signaling pathways; imatinib inhibits ERK and JNK phosphorylation and decreases c-Myc protein. MEK inhibitor (U0126), JNK inhibitor (SP600125), imatinib treatment; Western blot and proliferation assays in EOL-1 cells Biochemical and biophysical research communications Medium 18086564
2013 FIP1L1/PDGFRalpha (F/P) upregulates oncostatin M (OSM) expression in a STAT5-dependent manner; OSM produced by neoplastic eosinophils stimulates stromal cell proliferation and CXCL12 production, which in turn induces neoplastic eosinophil migration—establishing a paracrine loop. Lentiviral F/P transduction, doxycycline-inducible F/P expression in Ba/F3, gene expression analysis, cytokine assays, chemotaxis assays, immunohistochemistry of patient bone marrow Allergy Medium 23621172
2021 FIP1 (human FIP1L1) binds to the proximal polyadenylation signal (pPAS) of NLRP3 mRNA via its arginine-rich domain and induces 3'UTR shortening of NLRP3, upregulating NLRP3 expression; FIP1 is upregulated by oxidative stress and this upregulation amplifies NLRP3-driven inflammation and fibrogenesis in kidney injury. RNA immunoprecipitation, shRNA knockdown, in vivo UUO/IRI kidney injury models, NLRP3 3'UTR reporter assays Cell death & disease Medium 34011928
2005 Human Fip1 (hFip1) interacts specifically with U-rich upstream elements of the HPV-16 early polyadenylation signal region, enhancing polyadenylation at the early poly(A) site; deletion of this U-rich element reduces early poly(A) site utilization and increases late mRNA production. RNA-protein binding assay, deletion mutagenesis, polyadenylation reporter assays Journal of virology Medium 15767428

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. The New England journal of medicine 1311 12660384
2003 CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy. Blood 298 12842979
2004 FIP1L1-PDGFRA fusion: prevalence and clinicopathologic correlates in 89 consecutive patients with moderate to severe eosinophilia. Blood 246 15284118
2003 The FIP1L1-PDGFRalpha fusion tyrosine kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia: implications for diagnosis, classification, and management. Blood 212 15070659
2004 Human Fip1 is a subunit of CPSF that binds to U-rich RNA elements and stimulates poly(A) polymerase. The EMBO journal 209 14749727
2009 Frequent TET2 mutations in systemic mastocytosis: clinical, KITD816V and FIP1L1-PDGFRA correlates. Leukemia 203 19262599
2003 PKC412 overcomes resistance to imatinib in a murine model of FIP1L1-PDGFRα-induced myeloproliferative disease. Cancer cell 186 12781364
2007 Low-dose imatinib mesylate leads to rapid induction of major molecular responses and achievement of complete molecular remission in FIP1L1-PDGFRA-positive chronic eosinophilic leukemia. Blood 159 17299092
2007 The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRalpha-positive hypereosinophilic syndrome. Results of a multicenter prospective study. Haematologica 156 17666373
2014 Fip1 regulates mRNA alternative polyadenylation to promote stem cell self-renewal. The EMBO journal 139 24596251
2004 Clinical and molecular features of FIP1L1-PDFGRA (+) chronic eosinophilic leukemias. Leukemia 133 14973504
2007 Recurrent finding of the FIP1L1-PDGFRA fusion gene in eosinophilia-associated acute myeloid leukemia and lymphoblastic T-cell lymphoma. Leukemia 125 17377585
1995 The FIP1 gene encodes a component of a yeast pre-mRNA polyadenylation factor that directly interacts with poly(A) polymerase. Cell 123 7736590
2008 Five years since the discovery of FIP1L1-PDGFRA: what we have learned about the fusion and other molecularly defined eosinophilias. Leukemia 122 18843283
2006 Sorafenib is a potent inhibitor of FIP1L1-PDGFRalpha and the imatinib-resistant FIP1L1-PDGFRalpha T674I mutant. Blood 119 16645167
2006 FIP1L1-PDGFRA in eosinophilic disorders: prevalence in routine clinical practice, long-term experience with imatinib therapy, and a critical review of the literature. Leukemia research 107 16406016
2006 Activation of FIP1L1-PDGFRalpha requires disruption of the juxtamembrane domain of PDGFRalpha and is FIP1L1-independent. Proceedings of the National Academy of Sciences of the United States of America 101 16690743
2009 FIP1L1-PDGFRalpha D842V, a novel panresistant mutant, emerging after treatment of FIP1L1-PDGFRalpha T674I eosinophilic leukemia with single agent sorafenib. Leukemia 99 19212337
2005 The small molecule tyrosine kinase inhibitor AMN107 inhibits TEL-PDGFRbeta and FIP1L1-PDGFRalpha in vitro and in vivo. Blood 99 16030188
2003 The EOL-1 cell line as an in vitro model for the study of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia. Blood 85 14630792
2007 KIT D816V-associated systemic mastocytosis with eosinophilia and FIP1L1/PDGFRA-associated chronic eosinophilic leukemia are distinct entities. The Journal of allergy and clinical immunology 81 17628645
2008 A single weekly dose of imatinib is sufficient to induce and maintain remission of chronic eosinophilic leukaemia in FIP1L1-PDGFRA-expressing patients. British journal of haematology 67 18307562
2007 Molecular mechanisms underlying FIP1L1-PDGFRA-mediated myeloproliferation. Cancer research 62 17440089
2006 The FIP1L1-PDGFRA fusion gene cooperates with IL-5 to induce murine hypereosinophilic syndrome (HES)/chronic eosinophilic leukemia (CEL)-like disease. Blood 62 16418325
2005 A 57-nucleotide upstream early polyadenylation element in human papillomavirus type 16 interacts with hFip1, CstF-64, hnRNP C1/C2, and polypyrimidine tract binding protein. Journal of virology 62 15767428
2006 Multilineage involvement of the fusion gene in patients with FIP1L1/PDGFRA-positive hypereosinophilic syndrome. British journal of haematology 60 16409293
2004 The FIP1L1-PDGFRalpha kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia. Current opinion in hematology 57 14676627
2001 Fip1 regulates the activity of Poly(A) polymerase through multiple interactions. Molecular and cellular biology 57 11238938
2020 Epidemiology, clinical picture and long-term outcomes of FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia: Data from 151 patients. American journal of hematology 55 32720700
2005 The hypereosinophilic syndrome: fluorescence in situ hybridization detects the del(4)(q12)-FIP1L1/PDGFRA but not genomic rearrangements of other tyrosine kinases. Haematologica 51 15921374
2005 An Arabidopsis Fip1 homolog interacts with RNA and provides conceptual links with a number of other polyadenylation factor subunits. The Journal of biological chemistry 49 16282318
2012 Cyclin-dependent kinase 7/9 inhibitor SNS-032 abrogates FIP1-like-1 platelet-derived growth factor receptor α and bcr-abl oncogene addiction in malignant hematologic cells. Clinical cancer research : an official journal of the American Association for Cancer Research 47 22447844
2012 ETV6-PDGFRB and FIP1L1-PDGFRA stimulate human hematopoietic progenitor cell proliferation and differentiation into eosinophils: the role of nuclear factor-κB. Haematologica 43 22271894
2009 The fusion proteins TEL-PDGFRbeta and FIP1L1-PDGFRalpha escape ubiquitination and degradation. Haematologica 42 19644140
2004 FIP1L1-PDGFRA and c-kit D816V mutation-based clonality studies in systemic mast cell disease associated with eosinophilia. Haematologica 41 15257945
2009 Success of short-term, higher-dose imatinib mesylate to induce clinical response in FIP1L1-PDGFRalpha-negative hypereosinophilic syndrome. Leukemia research 40 19144405
2019 The polyadenylation factor FIP1 is important for plant development and root responses to abiotic stresses. The Plant journal : for cell and molecular biology 38 31111599
2010 FIP1/RCP binding to Golgin-97 regulates retrograde transport from recycling endosomes to the trans-Golgi network. Molecular biology of the cell 38 20610657
2021 Glioma glycolipid metabolism: MSI2-SNORD12B-FIP1L1-ZBTB4 feedback loop as a potential treatment target. Clinical and translational medicine 36 34047477
2007 The novel tyrosine kinase inhibitor EXEL-0862 induces apoptosis in human FIP1L1-PDGFR-alpha-expressing cells through caspase-3-mediated cleavage of Mcl-1. Leukemia 36 17495975
2006 Activity of AMN107, a novel aminopyrimidine tyrosine kinase inhibitor, against human FIP1L1-PDGFR-alpha-expressing cells. Leukemia research 35 16682077
2014 Identification of Ponatinib as a potent inhibitor of growth, migration, and activation of neoplastic eosinophils carrying FIP1L1-PDGFRA. Experimental hematology 34 24407160
2008 Detection and molecular monitoring of FIP1L1-PDGFRA-positive disease by analysis of patient-specific genomic DNA fusion junctions. Leukemia 34 18987650
2018 FIP1 Plays an Important Role in Nitrate Signaling and Regulates CIPK8 and CIPK23 Expression in Arabidopsis. Frontiers in plant science 32 29780398
2005 Idiopathic hypereosinophilic syndrome in children: report of a 7-year-old boy with FIP1L1-PDGFRA rearrangement. Journal of pediatric hematology/oncology 32 16344672
2006 The Rab11-FIP1/RCP gene codes for multiple protein transcripts related to the plasma membrane recycling system. Biochimica et biophysica acta 30 16920206
2006 Systemic mastocytosis (SM) associated with chronic eosinophilic leukemia (SM-CEL): detection of FIP1L1/PDGFRalpha, classification by WHO criteria, and response to therapy with imatinib. Leukemia research 29 16406018
2021 Alternative polyadenylation trans-factor FIP1 exacerbates UUO/IRI-induced kidney injury and contributes to AKI-CKD transition via ROS-NLRP3 axis. Cell death & disease 28 34011928
2006 Cough and hypereosinophilia due to FIP1L1-PDGFRA fusion gene with tyrosine kinase activity. The European respiratory journal 28 16387954
2012 Identification of JAK2 as a mediator of FIP1L1-PDGFRA-induced eosinophil growth and function in CEL. PloS one 27 22523564
2009 FIP1L1-PDGFRalpha imposes eosinophil lineage commitment on hematopoietic stem/progenitor cells. The Journal of biological chemistry 27 19147501
2008 Structure of yeast poly(A) polymerase in complex with a peptide from Fip1, an intrinsically disordered protein. Biochemistry 27 18537269
2016 Long-term outcomes of imatinib in patients with FIP1L1/ PDGFRA associated chronic eosinophilic leukemia: experience of a single center in China. Oncotarget 25 27120808
2008 The molecular anatomy of the FIP1L1-PDGFRA fusion gene. Leukemia 25 18987651
2013 The rab11 effector protein FIP1 regulates adiponectin trafficking and secretion. PloS one 24 24040321
2008 Dasatinib inhibits the growth and survival of neoplastic human eosinophils (EOL-1) through targeting of FIP1L1-PDGFRalpha. Experimental hematology 23 18619723
2021 Rab11-FIP1 mediates epithelial-mesenchymal transition and invasion in esophageal cancer. EMBO reports 21 33403789
2017 Structural basis of jasmonate-amido synthetase FIN219 in complex with glutathione S-transferase FIP1 during the JA signal regulation. Proceedings of the National Academy of Sciences of the United States of America 21 28223489
2007 The severity of FIP1L1-PDGFRA-positive chronic eosinophilic leukaemia is associated with polymorphic variation at the IL5RA locus. Leukemia 21 17914408
2014 Ponatinib efficiently kills imatinib-resistant chronic eosinophilic leukemia cells harboring gatekeeper mutant T674I FIP1L1-PDGFRα: roles of Mcl-1 and β-catenin. Molecular cancer 20 24472312
2009 A novel FIP1L1-PDGFRA mutant destabilizing the inactive conformation of the kinase domain in chronic eosinophilic leukemia/hypereosinophilic syndrome. Allergy 20 19210352
2014 FIP1L1 presence in FIP1L1-RARA or FIP1L1-PDGFRA differentially contributes to the pathogenesis of distinct types of leukemia. Annals of hematology 19 24763514
2006 Detection of the FIP1L1-PDGFRA fusion in idiopathic hypereosinophilic syndrome and chronic eosinophilic leukemia. Methods in molecular medicine 19 16502585
2011 A flexible linker region in Fip1 is needed for efficient mRNA polyadenylation. RNA (New York, N.Y.) 17 21282348
2010 Clinical characteristics of patients with chronic eosinophilic leukaemia (CEL) harbouring FIP1L1-PDGFRA fusion transcript--results of Polish multicentre study. Hematological oncology 17 19728396
2021 FIP1L1-PDGFRA-Associated Hypereosinophilic Syndrome as a Treatable Cause of Watershed Infarction. Stroke 16 34304603
2021 Dynamics in Fip1 regulate eukaryotic mRNA 3' end processing. Genes & development 16 34593603
2014 The tyrosine phosphatase SHP2 is required for cell transformation by the receptor tyrosine kinase mutants FIP1L1-PDGFRα and PDGFRα D842V. Molecular oncology 16 24618081
2009 FIP1L1-PDGFRA molecular analysis in the differential diagnosis of eosinophilia. BMC blood disorders 16 19187542
2009 Triptolide abrogates oncogene FIP1L1-PDGFRalpha addiction and induces apoptosis in hypereosinophilic syndrome. Cancer science 16 19671059
2014 Discovery of imatinib-responsive FIP1L1-PDGFRA mutation during refractory acute myeloid leukemia transformation of chronic myelomonocytic leukemia. Journal of hematology & oncology 15 24669761
2007 FIP1L1-PDGFRA in chronic eosinophilic leukemia and BCR-ABL1 in chronic myeloid leukemia affect different leukemic cells. Leukemia 15 17215855
2007 Synchronous FIP1L1-PDGFRA-positive chronic eosinophilic leukemia and T-cell lymphoblastic lymphoma: a bilineal clonal malignancy. European journal of haematology 15 18028420
2010 FIP1L1/PDGFR alpha-associated systemic mastocytosis. International archives of allergy and immunology 14 20523072
2023 The Arabidopsis pre-mRNA 3' end processing related protein FIP1 promotes seed dormancy via the DOG1 and ABA pathways. The Plant journal : for cell and molecular biology 13 37035898
2020 Molecular mechanism for the interaction between human CPSF30 and hFip1. Genes & development 13 33122294
2008 FIP1L1/PDGFRalpha synergizes with SCF to induce systemic mastocytosis in a murine model of chronic eosinophilic leukemia/hypereosinophilic syndrome. Blood 13 18539901
2022 Fip1 is a multivalent interaction scaffold for processing factors in human mRNA 3' end biogenesis. eLife 12 36073787
2017 Rab11-FIP1 phosphorylation by MARK2 regulates polarity in MDCK cells. Cellular logistics 12 28396819
2015 F604S exchange in FIP1L1-PDGFRA enhances FIP1L1-PDGFRA protein stability via SHP-2 and SRC: a novel mode of kinase inhibitor resistance. Leukemia 12 25761934
2013 The conformational control inhibitor of tyrosine kinases DCC-2036 is effective for imatinib-resistant cells expressing T674I FIP1L1-PDGFRα. PloS one 11 24009732
2006 Chronic eosinophilic leukemia with the FIP1L1-PDGFRalpha fusion gene in a patient with a history of combination chemotherapy. International journal of hematology 11 16513534
2015 Generalized Eruptive Histiocytosis Associated With FIP1L1-PDGFRA-Positive Chronic Eosinophilic Leukemia. JAMA dermatology 10 25923837
2014 Antitumor activity of S116836, a novel tyrosine kinase inhibitor, against imatinib-resistant FIP1L1-PDGFRα-expressing cells. Oncotarget 10 25431951
2013 Oncostatin M is a FIP1L1/PDGFRA-dependent mediator of cytokine production in chronic eosinophilic leukemia. Allergy 10 23621172
2007 A case of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia with a rare FIP1L1 breakpoint. The Journal of molecular diagnostics : JMD 10 17591942
2021 Rab11-FIP1 and Rab11-FIP5 Regulate pIgR/pIgA Transcytosis through TRIM21-Mediated Polyubiquitination. International journal of molecular sciences 9 34638806
2014 Complete and long-lasting cytologic and molecular remission of FIP1L1-PDGFRA-positive acute eosinophil myeloid leukaemia, treated with low-dose imatinib monotherapy. European journal of haematology 9 24460680
2007 A multicenter analysis of the FIP1L1-alphaPDGFR fusion gene in Japanese idiopathic hypereosinophilic syndrome: an aberrant splicing skipping the alphaPDGFR exon 12. Annals of hematology 9 17701174
2013 A case of nonleukemic myeloid sarcoma with FIP1L1-PDGFRA rearrangement: an unusual presentation of a rare disease. The American journal of surgical pathology 8 23232855
2011 Comparative proteomic analysis of blood eosinophils reveals redox signaling modifications in patients with FIP1L1-PDGFRA-associated chronic eosinophilic leukemia. Journal of proteome research 8 21302907
2009 The FIP-1 like polyadenylation factor in trypanosomes and the structural basis for its interaction with CPSF30. Biochemical and biophysical research communications 8 19338765
2008 Validation of a new three-color fluorescence in situ hybridization (FISH) method to detect CHIC2 deletion, FIP1L1/PDGFRA fusion and PDGFRA translocations. Leukemia research 8 19118897
2021 Myeloid Sarcoma Type of Acute Promyelocytic Leukemia With a Cryptic Insertion of RARA Into FIP1L1: The Clinical Utility of NGS and Bioinformatic Analyses. Frontiers in oncology 7 34249738
2017 A neoplasm with FIP1L1-PDGFRA fusion presenting as pediatric T-cell lymphoblastic leukemia/lymphoma without eosinophilia. Cancer genetics 7 29025601
2015 Refractory myeloid sarcoma with a FIP1L1-PDGFRA rearrangement detected by clinical high throughput somatic sequencing. Experimental hematology & oncology 7 26457233
2014 Hes1 upregulation contributes to the development of FIP1L1-PDGRA-positive leukemia in blast crisis. Experimental hematology 7 24486648
2008 FIP1L1-PDGFRalpha alone or with other genetic abnormalities reveals disease progression in chronic eosinophilic leukemia but good response to imatinib. Chinese medical journal 7 18706197
2007 Successful imatinib treatment of cardiac involvement of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia followed by severe hepatotoxicity. International journal of hematology 7 17988989
2007 Mechanisms for the proliferation of eosinophilic leukemia cells by FIP1L1-PDGFRalpha. Biochemical and biophysical research communications 7 18086564