Molecule Information

General Information of the Molecule (ID: Mol00590)

• Name: Ras association domain-containing protein 1 (RASSF1) ,Homo sapiens
• Synonyms: RDA32
• Molecule Type: Protein
• Gene Name: RASSF1
• Gene ID: 11186
• Location: chr3:50329782-50340980[-]
• Sequence:
  MSGEPELIELRELAPAGRAGKGRTRLERANALRIARGTACNPTRQLVPGRGHRFQPAGPA
  THTWCDLCGDFIWGVVRKGLQCARLSADCKFTCHYRCRALVCLDCCGPRDLGWEPAVERD
  TNVDEPVEWETPDLSQAEIEQKIKEYNAQINSNLFMSLNKDGSYTGFIKVQLKLVRPVSV
  PSSKKPPSLQDARRGPGRGTSVRRRTSFYLPKDAVKHLHVLSRTRAREVIEALLRKFLVV
  DDPRKFALFERAERHGQVYLRKLLDDEQPLRLRLLAGPSDKALSFVLKENDSGEVNWDAF
  SMPELHNFLRILQREEEEHLRQILQKYSYCRQKIQEALHACPLG
• Function: Potential tumor suppressor. Required for death receptor-dependent apoptosis. Mediates activation of STK3/MST2 and STK4/MST1 during Fas-induced apoptosis by preventing their dephosphorylation. When associated with MOAP1, promotes BAX conformational change and translocation to mitochondrial membranes in response to TNF and TNFSF10 stimulation. Isoform A interacts with CDC20, an activator of the anaphase-promoting complex, APC, resulting in the inhibition of APC activity and mitotic progression. Inhibits proliferation by negatively regulating cell cycle progression at the level of G1/S-phase transition by regulating accumulation of cyclin D1 protein. Isoform C has been shown not to perform these roles, no function has been identified for this isoform. Isoform A disrupts interactions among MDM2, DAXX and USP7, thus contributing to the efficient activation of TP53 by promoting MDM2 self-ubiquitination in cell-cycle checkpoint control in response to DNA damage.
• Uniprot ID: RASF1_HUMAN
• Ensembl ID: ENSG00000068028
• HGNC ID: HGNC:9882

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

Type(s) of Resistant Mechanism of This Molecule

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Germ cell tumor [1]

• Resistant Disease: Germ cell tumor [ICD-11: 2D12.Y]
• Resistant Drug: Cisplatin
• Molecule Alteration: Methylation; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: 833K-E cells; Ascites; Homo sapiens (Human); CVCL_2292
• Experiment for Molecule Alteration: Western blotting assay
• Mechanism Description: Promoter hypermethylation of RASSF1A and HIC1 genes play a role in resistance of GCT, while the transcriptional inactivation of MGMT by epigenetic alterations confer exquisite sensitivity to cisplatin.

Sorafenib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Hepatocellular carcinoma [2]

• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Sensitive Drug: Sorafenib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: MAPK signaling pathway; Inhibition; hsa04010
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Caspase 3/7 activity analysis; CCK8 assay
• Mechanism Description: miR-181a induces sorafenib resistance of hepatocellular carcinoma cells through downregulation of RASSF1 expression.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Liver cancer [ICD-11: 2C12]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Liver
• The Specified Disease: Liver cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.26E-03; Fold-change: 1.65E-01; Z-score: 4.92E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 4.63E-02; Fold-change: -1.32E-01; Z-score: -2.61E-01
• The Expression Level of Disease Section Compare with the Other Disease Section: p-value: 4.31E-01; Fold-change: 2.72E-01; Z-score: 3.70E-01

References

• Ref 1: Role of promoter hypermethylation in Cisplatin treatment response of male germ cell tumors .Mol Cancer. 2004 May 18;3:16. doi: 10.1186/1476-4598-3-16. 10.1186/1476-4598-3-16
• Ref 2: miR-181a induces sorafenib resistance of hepatocellular carcinoma cells through downregulation of RASSF1 expression. Cancer Sci. 2016 Sep;107(9):1256-62. doi: 10.1111/cas.13006. Epub 2016 Sep 2.