Recombinant Human RAF proto-oncogene serine/threonine-protein kinase(RAF1)

1. The functional assessment supported the pathogenicity of the RAF1 and RIT1 VUSs, while the significance of two variants of unknown significance in A2ML1 remained unclear. PMID: 29402968
2. Our report presents the second familial case of Noonan syndrome due to a germline p.S427G substitution in RAF] with no occurrence of a malignant tumor. It may suggest that carrying a germline mutation in the RAF1 oncogene is not associated with an increased risk of tumor development. Since RAF1 mutations have been observed as a somatic event in many types of cancer. PMID: 30204961
3. Data indicate that Raf-1 proto-oncogene, serine-threonine kinase (RAF1) is a negative regulator of hepatocarcinogenesis. PMID: 28000790
4. we report a patient with an inherited RAF1-associated Noonan syndrome, presenting with an antenatally diagnosed abnormality of skull shape, bilateral subdural haematomas, of unknown cause, delayed myelination and polymicrogyria. PMID: 27753652
5. Raf1 may serve as a novel prognostic factor and potential target for improving the longterm outcome of nonsmall cell lung cancer (NSCLC). PMID: 29484414
6. Results provide evidence that RAF1 binding to SPRY4 is regulated by miR-1908 in glioma tumors. PMID: 29048686
7. High RAF1 expression is associated with malignant melanoma. PMID: 28677804
8. two premature neonates with progressive biventricular hypertrophy found to have RAF1 variants in the CR2 domain, are reported. PMID: 28777121
9. Data indicate connector enhancer of kinase suppressor of Ras 1 protein (CNK1) as a molecular platform that controls c-raf protein (RAF) and c-akt protein (AKT) signalling and determines cell fate decisions in a cell type- and cell stage-dependent manner. PMID: 27901111
10. CRAF is a bona fide alternative oncogene for BRAF/NRAS/GNAQ/GNA11 wild type melanomas PMID: 27273450
11. Authors evaluated the expression of known targets of miR-125a and found that sirtuin-7, matrix metalloproteinase-11, and c-Raf were up-regulated in tumor tissue by 2.2-, 3-, and 1.7-fold, respectively. Overall, these data support a tumor suppressor role for miR-125a. PMID: 28445974
12. Overexpression of ciRS-7 in HCT116 and HT29 cells led to the blocking of miR-7 and resulted in a more aggressive oncogenic phenotype, and ciRS-7 overexpression permitted the inhibition of miR-7 and subsequent activation of EGFR and RAF1 oncogenes PMID: 28174233
13. miR-497 could serve as a tumor suppressor and a potential early diagnostic marker of gastric cancer by targeting Raf-1 proto-oncogene. PMID: 28586056
14. RAF1 may have a role in survival in hepatocellular carcinoma, and indicate whether sorafenib should be used as a postoperative adjuvant PMID: 26981887
15. Mutational activation of Kit-, Ras/Raf/Erk- and Akt- pathways indicate the biological importance of these pathways and their components as potential targets for therapy. PMID: 27391150
16. Results indicate that des-gamma-carboxy prothrombin (DCP) antagonizes the inhibitory effects of Sorafenib on hepatocellular carcinoma (HCC) through activation of the Raf/MEK/ERK and PI3K/Akt/mTOR signaling pathways. PMID: 27167344
17. DiRas3 binds to KSR1 independently of its interaction with activated Ras and RAF. PMID: 27368419
18. RhoA/ROCK and Raf-1/CK2 pathway are responsible for TNF-alpha-mediated endothelial cytotoxicity via regulation of the vimentin cytoskeleton. PMID: 28743511
19. Although Raf-1 gene is not mutated, an abnormality of Raf-1 kinase feedback regulation enhances its antiapoptotic function, and Raf-1 can still be a pharmaceutical target to increase chemotherapy or radiotherapy sensitivity in these cancer cells. PMID: 27841865
20. RAF1 plays a critical role in maintaining the transformed phenotype of CRC cells, including those with mutated KRAS. PMID: 27670374
21. This finding suggests that stringent assemblage of Hsp90 keeps CRAF kinase equipped for participating in the MAPK pathway. Thus, the role of Hsp90 in CRAF maturation and activation acts as a limiting factor to maintain the function of a strong client like CRAF kinase. PMID: 27703006
22. Oncogenic NFIA:RAF1 fusion activation of the MAPK pathway is associated with pilocytic astrocytoma. PMID: 27810072
23. IGF2BP2 as a post-transcriptional regulatory mRNA-binding factor, interfering with Raf-1 degradation by miR-195, that contributes to Colorectal carcinogenesis. PMID: 27153315
24. Data show that when microRNA miR-125b was over-expressed in THP-1 macrophages, the expression of Raf1 proto-oncogene serine/threonine protein kinase (RAF1) was reduced to promote the apoptosis of macrophages. PMID: 27363278
25. Data show that Griffipavixanthone (GPX), a dimeric xanthone isolated from Garcinia esculenta, is a B-RAF and C-RAF inhibitor against esophageal cancer cells. PMID: 26646323
26. Up-regulation of Raf-1 is associated with triple-negative breast cancer. PMID: 26513016
27. This study provides the molecular basis for C-Raf C-terminal-derived phosphopeptide interaction with 14-3-3zeta protein and gives structural insights responsible for phosphorylation-mediated protein binding. PMID: 26295714
28. a model that CD166 regulates MCAM through a signaling flow from activation of PI3K/AKT and c-Raf/MEK/ERK signaling to the inhibition of potential MCAM ubiquitin E3 ligases, betaTrCP and Smurf1. PMID: 26004137
29. Suggest an interrelated kinase module involving c-Raf/PI3K/Lyn and perhaps Fgr functions in a nontraditional way during retinoic acid-induced maturation or during rescue of RA induction therapy using inhibitor co-treatment in RA-resistant leukemia cells. PMID: 25817574
30. Abnormal activation of the Ras/MAPK pathway may play a significant role in the development of pulmonary vascular disease in the subset of patients with Noonan syndrome and a specific RAF1 mutation. PMID: 25706034
31. Raf-1 may be an important biomarker in predicting the prognosis of chordoma patients. PMID: 25755752
32. In the presence of Raf1, the RasQ61L mutant has a rigid switch II relative to the wild-type and increased flexibility at the interface with switch I, which propagates across Raf-Ras binding domain. PMID: 25684575
33. Besides mediating the anticancer effect, pDAPK(S308) may serve as a predictive biomarker for Raf inhibitors combination therapy, suggesting an ideal preclinical model that is worthy of clinical translation. PMID: 26100670
34. DJ-1 directly binds to the kinase domain of c-Raf to stimulate its self-phosphorylation, followed by phosphorylation of MEK and ERK1/2 in EGF-treated cells. PMID: 26048984
35. truncated RAF1 and BRAF proteins, recently described as products of genomic rearrangements in gastric cancer and other malignancies, have the ability to render neoplastic cells resistant to RTK-targeted therapy PMID: 25473895
36. our study demonstrated that miR-455-RAF1 may represent a new potential therapeutic target for colorectal carcinoma treatment. PMID: 25355599
37. approach identified 18 kinase and kinase-related genes whose overexpression can substitute for EGFR in EGFR-dependent PC9 cells, and these genes include seven of nine Src family kinase genes, FGFR1, FGFR2, ITK, NTRK1, NTRK2, MOS, MST1R, and RAF1. PMID: 25512530
38. Aberrant expression of A-, B-, and C-RAF, and COT is frequent in PTC; increased expression of COT is correlated with recurrence of PTC. PMID: 25674762
39. Authors demonstrate that the N-terminus of human Raf1 kinase (hRaf11-147aa) binds with human RKIP (hRKIP) at its ligand-binding pocket, loop "127-149", and the C-terminal helix by nuclear magnetic resonance experiments. PMID: 24863296
40. Including several anti-apoptotic Bcl-2 family members and c-Raf. PMID: 24969872
41. These data suggest that miR-7-5p functions as a tumor suppressor gene to regulate glioblastoma microvascular endothelial cell proliferation potentially by targeting the RAF1 oncogene PMID: 25027403
42. A novel mechanism for response was discovered whereby high expression level of CAV-1 at the plasma membrane disrupts the BRaf/CRaf heterodimer and thus inhibits the activation of MAPK pathway during dasatinib treatment. PMID: 24486585
43. Results show that ubiquitination and levels of RAF-1 is controlled by both Shoc2 and HUWE1. PMID: 25022756
44. Raf-1/JNK /p53/p21 pathway may be involved in apoptosis, and NFkappaB1 may play a possible role in inhibiting apoptosis. PMID: 22282237
45. The higher expression of RAF1 mRNA and the activation of AKT/ERK proteins in vinorelbine-resistant non-small cell lung cancer cell lines may confer resistance to vinorelbine PMID: 24427333
46. analysis of RAF1 mutations in cohorts of South Indian, North Indian and Japanese patients with childhood-onset dilated cardiomyopathy PMID: 24777450
47. Expression of miR-195 or knockdown of Raf-1 can similarly reduce tumor cell survival. PMID: 23760062
48. We hypothesize a potential direct or indirect role for SRC, RAF1, PTK2B genes in neurotransmission and in central nervous system signaling processes. PMID: 24108181
49. we identified multiple C-RAF mutations that produced biochemical and pharmacologic resistance in melanoma cell lines PMID: 23737487
50. ARAF seems to stabilize BRAF:CRAF complexes in cells treated with RAF inhibitors and thereby regulate cell signaling in a subtle manner to ensure signaling efficiency PMID: 22926515
51. Aberrant BRAF splice variants with deletions in both kinase and RAS-binding domains in rheumatoid arthritis patients demonstrate that these BRAF splice variants constitutively activate MAPK through CRAF PMID: 23517740
52. Antisense oligonucleotides targeting BCL-2 and C-RAF transcripts in tumor cell lines increases sensitivity to cytotoxic effect of etoposide. PMID: 23610963
53. these findings establish RanBPM as a novel inhibitor of the ERK pathway through an interaction with the c-Raf complex and a regulation of c-Raf stability PMID: 23118896
54. Gefitinib reverses the MDR protein gene expression and restores sensitivity of pancreatic cancer cells resistant to gemcitabine via RAF1/ERK signaling pathway. PMID: 22907845
55. Ras pathway activation via EGF treatment induced strong binding between B-Raf and C-Raf and a low level of binding between B-Raf and A-Raf. PMID: 23352452
56. osteosarcoma patients whose tumors expressed raf-1 had a poorer clinical outcome than those whose tumors did not. PMID: 22935974
57. Investigated BRAF and RAF1 alterations in Chinese prostate cancer.Found BRAF truncated in five of 200 informative Chinese cases & RAF1 was truncated in three of 204 informative cases and genomic rearrangements were correlated w/high Gleason scores. PMID: 22833462
58. results suggest a novel mechanism that the interaction of Raf-1 with cytoskeletal actin is critical for Raf-1 redistribution and airway smooth muscle cell proliferation during activation with the growth factor PMID: 23087049
59. The dominant effect of prolonged USP15 depletion upon signal amplitude is due to a decrease in CRAF levels while allowing for the possibility that USP15 may also function to dampen MAPK signaling through direct stabilization of BRAP. PMID: 23105109
60. Data indicate that erufosine caused dose-dependent decreases in the phosphorylation of PI3K (p85), Akt (PKB) at Thr 308 and cRaf in both MCF-7 and MDA-MB 231 cell lines. PMID: 22752602
61. Determination of a 1:1 stoichiometry for the diphosphorylated peptide binding to one 14-3-3zeta dimer with isothermal titration calorimetry was supported by the crystal structure of the 14-3-3zeta/C-RAFpS233,pS259 complex. PMID: 22922483
62. Cellular Raf-1 levels determine endometrial stromal cell motility and morphology. PMID: 22225925
63. Raf-1 over-expression was an independent prognostic factor of poor survival in hepatocellular carcinoma. PMID: 20868603
64. These findings demonstrate that overexpression of Raf-1, p-Raf-1 or both could be considered as a new independent prognostic biomarker for poor survival rates for non-small cell lung cancer patients PMID: 22738312
65. RAF1(D486N), as well as other kinase-impaired RAF1 mutants, showed increased heterodimerization with BRAF, which was necessary and sufficient to promote increased MEK/ERK activation. PMID: 22826437
66. unknown role for ML-IAP in controlling C-RAF stability and cell migration. PMID: 22711539
67. PP242 mTOR inhibitor activates ERK in multiple myeloma cells via a target of rapamycin complex 1 (TORC1)/eukaryotic translation initiation factor 4E (eIF-4E)/RAF pathway and activation is a mechanism of resistance PMID: 22556409
68. The consequence of complex formation is a DiRas3-mediated recruitment and anchorage of C-RAF to components of the membrane skeleton, suppression of C-RAF/B-RAF heterodimerization, and inhibition of C-RAF kinase activity. PMID: 22605333
69. RKIP expression may serve as a novel clinical biomarker in patients with esophageal squamous cell carcinoma. PMID: 22464151
70. These results demonstrate that replicative and oxidative stresses are not required for RAF-induced senescence, and this senescence is readily reversed upon loss of cyclin-dependent kinases. PMID: 22020327
71. Data show that bilirubin interacts with the Raf/ERK/MAPK pathway, effect on cyclin D1 and Raf content, altered retinoblastoma protein profile of hypophosphorylation, calcium influx, and YY1 proteolysis. PMID: 22262839
72. amplification of Raf1, MEK/MAPK oncogenic signaling during tumor growth promotes the genesis of metastatic lesions from primary tumors by activating the mesenchymal epithelial transition. PMID: 22447278
73. Interleukin-6, osteopontin and Raf/MEK/ERK signaling modulate the sensitivity of human myeloma cells to alkylphosphocholines. PMID: 22421411
74. ndings demonstrate that Pak1 phosphorylates BAD directly at S111, but phosphorylated S112 through Raf-1. PMID: 22096607
75. Conditional expression of oncogenic C-RAF in mouse pulmonary epithelial cells reveals differential tumorigenesis and induction of autophagy leading to tumor regression. PMID: 22131876
76. LEOPARD syndrome, both with proven mutations in the RAF1 gene not previouslyreported PMID: 22389993
77. Ras/Raf-1/MEK/ERK signal pathway is important for chemokine ligand CCL2-induced migration activity and matrix metalloproteinase (MMP)-9 expression. PMID: 22138288
78. High RAF1 is associated with hepatocellular carcinoma. PMID: 22110214
79. CRAF is required for mitotic progression. Phospho-Ser338 CRAF is upregulated in mitosis and localizes to the mitotic spindles in human cell lines and tumor biopsies. PMID: 22081024
80. Report cooperative effects of Akt-1 and Raf-1 on the induction of cellular senescence in doxorubicin or tamoxifen treated breast cancer cells. PMID: 21881167
81. Studies indicate that Raf kinases are excellent molecular targets for anticancer therapy. PMID: 21577205
82. Raf-1 was dominant in terms of promoting both cell cycle progression and preventing apoptosis when compared to Akt-1 PMID: 20372086
83. Downregulation of RKIP increased the level of free Raf-1 and thereby elevated the mitochondrial translocation of Raf-1 during HBx-mediated hepatocarcinogenesis. PMID: 21617351
84. c-Raf plays a unique role in mediating K-Ras signaling in non-small cell lung carcinoma and makes it a suitable target for therapeutic intervention. PMID: 21514245
85. Hepatitis B virus could up-regulate Raf1 expression by enhancing the activity of its promoter in a dose-dependent manner, and HBs and HBx may be involved in this process. PMID: 21207082
86. EZH2 expression-mediated downregulation of DNA damage repair leads to accumulation of recurrent RAF1 gene amplification in breast tumor initiating cells (BTICs), which activates p-ERK-beta-catenin signaling to promote BTIC expansion. PMID: 21215703
87. Findings suggest that modulating the C-RAFSer(259)/14-3-3 protein-protein interaction with a stabilizing small molecule may yield a novel potential approach for treatment of diseases resulting from an overactive Ras-RAF-MAPK pathway. PMID: 20679480
88. Reduction in Raf-1 kinase inhibitory protein expression in gallbladder carcinoma contributes to invasion and metastasis and is a significant prognostic marker in patients with gallbladder carcinoma. PMID: 20688353
89. dephosphorylation of S259 is the primary pathogenic mechanism in the activation of RAF1 mutants located in the CR2 domain as well as of downstream ERK PMID: 20052757
90. Results suggest that RAGE, NOX, and H-Ras/Raf-1 are implicated in the up-regulation of HSF1 or PAI-1 in vascular EC under diabetes-associated metabolic stress. PMID: 20630999
91. Results indicate that the Shoc2 scaffold protein modulates Ras-dependent Raf1 activation in a Ca(2+)- and calmodulin-dependent manner. PMID: 20071468
92. Data show that RAF not only neutralizes BAD's pro-apoptotic activity but activates it for a new function as a pore. PMID: 19895838
93. Based on our results, it is possible that a subtle dysfunction (expression) of the RAF1 gene is involved in the development of the most common male reproductive tract disorder - unilateral or bilateral cryptorchidism PMID: 20389169
94. Infection with Chlamydia trachomatis led to the Akt-dependent, increased phosphorylation (and inactivation) of Raf-1 at serine-259. PMID: 20234004
95. Study demonstrates that human TAP-1 regulates signaling in vertebrate cells, acting at a previously uncharacterized step of the Ras pathway by inhibiting the ability of Raf to translocate to activated Ras at the cell membrane. PMID: 20230813
96. The C-Raf expression is up-regulated in a subset of melanomas but not in nevi, suggesting that it might be a valuable diagnostic marker and therapeutic target. PMID: 19737955
97. analysis of molecular pertubations allowing dysplasia to progress further to adenocarcinoma induced by exaggerted c-Raf kinase activity PMID: 19812696
98. Noonan syndrome (NS) is an autosomal dominant disorder caused by mutations in several proteins, including RAF1, which may later involve tumor onsets. PMID: 19953625
99. Thus, the short hairpin-looped ODN-Raf, targeting the same region of c-raf-1 as miR-125b, is a multifunctional molecule reducing the expression of oncoproteins and stimulating cell death. PMID: 19825990
100. Bcl-2-associated anthanogene 1 (BAG-1)'s effects were associated with an activation of RAF-1-a known binding partner of BAG-1, enhanced signaling through the MAP kinase pathway and a decrease in BIM expression. PMID: 19881545

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HGNC: 9829

OMIM: 164760

KEGG: hsa:5894

STRING: 9606.ENSP00000251849

UniGene: Hs.159130