Molecule Information

General Information of the Molecule (ID: Mol04345)

Name	Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) ,Homo sapiens
Synonyms	Tumor necrosis factor receptor 1; Tumor necrosis factor receptor type I; p55; p60; CD_antigen=CD120a Click to Show/Hide
Molecule Type	Protein
Gene Name	TNFRSF1A
Gene ID	7132
Sequence	MGLSTVPDLLLPLVLLELLVGIYPSGVIGLVPHLGDREKRDSVCPQGKYIHPQNNSICCT KCHKGTYLYNDCPGPGQDTDCRECESGSFTASENHLRHCLSCSKCRKEMGQVEISSCTV D RDTVCGCRKNQYRHYWSENLFQCFNCSLCLNGTVHLSCQEKQNTVCTCHAGFFLRENE CV SCSNCKKSLECTKLCLPQIENVKGTEDSGTTVLLPLVIFFGLCLLSLLFIGLMYRYQ RWK SKLYSIVCGKSTPEKEGELEGTTTKPLAPNPSFSPTPGFTPTLGFSPVPSSTFTSS STYT PGDCPNFAAPRREVAPPYQGADPILATALASDPIPNPLQKWEDSAHKPQSLDTDD PATLY AVVENVPPLRWKEFVRRLGLSDHEIDRLELQNGRCLREAQYSMLATWRRRTPRR EATLEL LGRVLRDMDLLGCLEDIEEALCGPAALPPAPSLLR Click to Show/Hide
Function	Receptor for TNFSF2/TNF-alpha and homotrimericTNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8to the activated receptor. The resulting death-inducing signalingcomplex performs caspase-8 proteolytic activation whichinitiates the subsequent cascade of caspases mediating apoptosis. Contributes to the inductionof non-cytocidal TNF effects including anti-viral state and activationof the acid sphingomyelinase. Click to Show/Hide
Uniprot ID	TNR1A_HUMAN
Ensembl ID	ENSG000000671829
HGNC ID	HGNC:11916
*Click to Show/Hide the Complete Species Lineage*
Kingdom: Metazoa Phylum: Chordata Class: Mammalia Order: Primates Family: Hominidae Genus: Homo Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

RTDM: Regulation by the Disease Microenvironment

Drug Resistance Data Categorized by Drug

Approved Drug(s)

1 drug(s) in total

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Bortezomib

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Regulation by the Disease Microenvironment (RTDM)			Click to Show/Hide
Disease Class: Multiple myeloma [ICD-11: 2A83.0]				[1]
Resistant Disease	Multiple myeloma [ICD-11: 2A83.0]			Disease Info
Resistant Drug	Bortezomib			Drug Info
Molecule Alteration	Expression		Up-regulation
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	NCI-H929 cells	Bone marrow	Homo sapiens (Human)	CVCL_1600
Experiment for Molecule Alteration	Western blot assay
Experiment for Drug Resistance	MTT assay
Mechanism Description	In particular, the dynamic interaction between BM mesenchymal stem cells (BM-MSC) and MM cells has shown great relevance. Here we showed that inhibiting both PKC and NF-kappaB signalling pathways in BM-MSC reduced cell survival in the MM cell line H929 and increased its susceptibility to the proteasome inhibitor bortezomib. PKC-mediated cell survival inhibition and bortezomib susceptibility induction were better performed by the chimeric peptide HKPS than by the classical enzastaurin inhibitor, probably due to its greatest ability to inhibit cell adhesion and its increased capability to counteract the NF-kappaB-related signalling molecules increased by the co-cultivation of BM-MSC with H929 cells. Thus, inhibiting two coupled signalling molecules in BM-MSC was more effective in blocking the supportive cues emerging from the mesenchymal stroma.

References

Ref 1	Simultaneously Targeting Two Coupled Signalling Molecules in the Mesenchymal Stem Cell Support Efficiently Sensitises the Multiple Myeloma Cell Line H929 to Bortezomib. Int J Mol Sci. 2023 May 2;24(9):8157.