Molecule Information

General Information of the Molecule (ID: Mol01911)

• Name: REL proto-oncogene, NF-kB subunit (REL) ,Homo sapiens
• Synonyms: REL
• Molecule Type: Protein
• Gene Name: REL
• Gene ID: 5966
• Location: chr2:60,881,521-60,931,612[+]
• Sequence:
  MASGAYNPYIEIIEQPRQRGMRFRYKCEGRSAGSIPGEHSTDNNRTYPSIQIMNYYGKGK
  VRITLVTKNDPYKPHPHDLVGKDCRDGYYEAEFGQERRPLFFQNLGIRCVKKKEVKEAII
  TRIKAGINPFNVPEKQLNDIEDCDLNVVRLCFQVFLPDEHGNLTTALPPVVSNPIYDNRA
  PNTAELRICRVNKNCGSVRGGDEIFLLCDKVQKDDIEVRFVLNDWEAKGIFSQADVHRQV
  AIVFKTPPYCKAITEPVTVKMQLRRPSDQEVSESMDFRYLPDEKDTYGNKAKKQKTTLLF
  QKLCQDHVETGFRHVDQDGLELLTSGDPPTLASQSAGITVNFPERPRPGLLGSIGEGRYF
  KKEPNLFSHDAVVREMPTGVSSQAESYYPSPGPISSGLSHHASMAPLPSSSWSSVAHPTP
  RSGNTNPLSSFSTRTLPSNSQGIPPFLRIPVGNDLNASNACIYNNADDIVGMEASSMPSA
  DLYGISDPNMLSNCSVNMMTTSSDSMGETDNPRLLSMNLENPSCNSVLDPRDLRQLHQMS
  SSSMSAGANSNTTVFVSQSDAFEGSDFSCADNSMINESGPSNSTNPNSHGFVQDSQYSGI
  GSMQNEQLSDSFPYEFFQV
• Function: Proto-oncogene that may play a role in differentiation and lymphopoiesis. NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. The NF-kappa-B heterodimer RELA/p65-c-Rel is a transcriptional activator.
• Uniprot ID: REL_HUMAN
• Ensembl ID: ENSG00000162924
• HGNC ID: HGNC:9954

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Investigative Drug(s) 1 drug(s) in total

PLX51107

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Uveal melanoma [1]

• Sensitive Disease: Uveal melanoma [ICD-11: 2D0Y.0]
• Sensitive Drug: PLX51107
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: NF-kappaB signaling pathway; Inhibition; hsa04064
• In Vitro Model: Omm1.3 cells; Skin; Homo sapiens (Human); N.A.
• In Vitro Model: 92.1 cells; Peripheral blood; Homo sapiens (Human); N.A.
• In Vitro Model: UM004 cells; Skin; Homo sapiens (Human); N.A.
• In Vitro Model: Omm1 cells; Kidney; Homo sapiens (Human); CVCL_6939
• In Vivo Model: Athymic nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR; Western blotting assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Both assays showed higher expression of these genes(REL, RELB, CEBPD, SOD2) at the mRNA and protein level in the resistant cells compared with their parental counterpart. Furthermore, NF-kappa-B activity was increased in the resistant cells compared with parental, and it could be inhibited by PTL.Inhibition of NF-kappa-B-dependent signaling enhances sensitivity and overcomes resistance to BET inhibition in uveal melanoma.

References

• Ref 1: Inhibition of NF-kB-Dependent Signaling Enhances Sensitivity and Overcomes Resistance to BET Inhibition in Uveal Melanoma .Cancer Res. 2019 May 1;79(9):2415-2425. doi: 10.1158/0008-5472.CAN-18-3177. Epub 2019 Mar 18. 10.1158/0008-5472.CAN-18-3177