Molecule Information

General Information of the Molecule (ID: Mol01912)

• Name: RELB proto-oncogene, NF-kB subunit (RELB) ,Homo sapiens
• Synonyms: RELB
• Molecule Type: Protein
• Gene Name: RELB
• Gene ID: 5971
• Location: chr19:45,001,449-45,038,198[+]
• Sequence:
  MLRSGPASGPSVPTGRAMPSRRVARPPAAPELGALGSPDLSSLSLAVSRSTDELEIIDEY
  IKENGFGLDGGQPGPGEGLPRLVSRGAASLSTVTLGPVAPPATPPPWGCPLGRLVSPAPG
  PGPQPHLVITEQPKQRGMRFRYECEGRSAGSILGESSTEASKTLPAIELRDCGGLREVEV
  TACLVWKDWPHRVHPHSLVGKDCTDGICRVRLRPHVSPRHSFNNLGIQCVRKKEIEAAIE
  RKIQLGIDPYNAGSLKNHQEVDMNVVRICFQASYRDQQGQMRRMDPVLSEPVYDKKSTNT
  SELRICRINKESGPCTGGEELYLLCDKVQKEDISVVFSRASWEGRADFSQADVHRQIAIV
  FKTPPYEDLEIVEPVTVNVFLQRLTDGVCSEPLPFTYLPRDHDSYGVDKKRKRGMPDVLG
  ELNSSDPHGIESKRRKKKPAILDHFLPNHGSGPFLPPSALLPDPDFFSGTVSLPGLEPPG
  GPDLLDDGFAYDPTAPTLFTMLDLLPPAPPHASAVVCSGGAGAVVGETPGPEPLTLDSYQ
  APGPGDGGTASLVGSNMFPNHYREAAFGGGLLSPGPEAT
• Function: 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. NF-kappa-B heterodimeric RelB-p50 and RelB-p52 complexes are transcriptional activators. RELB neither associates with DNA nor with RELA/p65 or REL. Stimulates promoter activity in the presence of NFKB2/p49. As a member of the NUPR1/RELB/IER3 survival pathway, may provide pancreatic ductal adenocarcinoma with remarkable resistance to cell stress, such as starvation or gemcitabine treatment. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer in a CRY1/CRY2 independent manner. Increased repression of the heterodimer is seen in the presence of NFKB2/p52. Is required for both T and B lymphocyte maturation and function.
• Uniprot ID: RELB_HUMAN
• Ensembl ID: ENSG00000104856
• HGNC ID: HGNC:9956

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