Molecule Information

General Information of the Molecule (ID: Mol04355)

• Name: M-phase inducer phosphatase 2 (CDC25B) ,Homo sapiens
• Synonyms: Dual specificity phosphatase Cdc25B
• Molecule Type: Protein
• Gene Name: CDC25B
• Gene ID: 994
• Sequence:
  MEVPQPEPAPGSALSPAGVCGGAQRPGHLPGLLLGSHGLLGSPVRAAASSPVTTLTQTMH
  DLAGLGSETPKSQVGTLLFRSRSRLTHLSLSRRASESSLSSESSESSDAGLCMDSPSPM
  D PHMAEQTFEQAIQAASRIIRNEQFAIRRFQSMPVRLLGHSPVLRNITNSQAPDGRRKS
  EA GSGAASSSGEDKENDGFVFKMPWKPTHPSSTHALAEWASRREAFAQRPSSAPDLMCL
  SPD RKMEVEELSPLALGRFSLTPAEGDTEEDDGFVDILESDLKDDDAVPPGMESLISAP
  LVKT LEKEEEKDLVMYSKCQRLFRSPSMPCSVIRPILKRLERPQDRDTPVQNKRRRSVT
  PPEEQ QEAEEPKARVLRSKSLCHDEIENLLDSDHRELIGDYSKAFLLQTVDGKHQDLKY
  ISPETM VALLTGKFSNIVDKFVIVDCRYPYEYEGGHIKTAVNLPLERDAESFLLKSPIA
  PCSLDKR VILIFHCEFSSERGPRMCRFIRERDRAVNDYPSLYYPEMYILKGGYKEFFPQ
  HPNFCEPQ DYRPMNHEAFKDELKTFRLKTRSWAGERSRRELCSRLQDQ
• Function: Tyrosine protein phosphatase which functions as a dosage-dependent inducer of mitotic progression . Directly dephosphorylates CDK1 and stimulates itskinase activity . Required for G2/M phases of the cellcycle progression and abscission during cytokinesis in a ECT2-dependentmanner . The three isoforms seem to have a differentlevel of activity . {ECO:0000269|PubMed:17332740,ECO:0000269|PubMed:1836978, ECO:0000269|PubMed:20360007}.
• Uniprot ID: MPIP2_HUMAN
• Ensembl ID: ENSG0000010122418
• HGNC ID: HGNC:1726

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

Drug Resistance Data Categorized by Drug

Clinical Trial Drug(s) 1 drug(s) in total

JQ1

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0] [1]

• Sensitive Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Sensitive Drug: JQ1
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Panc1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• In Vitro Model: MiaPaCa-2 cells; Blood; Homo sapiens (Human); CVCL_0428
• In Vitro Model: BxPc3 cells; Pancreas; Homo sapiens (Human); CVCL_0186
• In Vivo Model: SCID CB 17-/- female mice model; Mus musculus
• Experiment for Molecule Alteration: Immunohistochemistry; Immunoblotting assay
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Results: Immunohistochemical data demonstrated that levels of CDC25B differed by ~2- to 5-fold in cell lines and PDX models used. In vitro data showed that the level of CDC25B paralleled sensitivity to JQ1. Similarly, in vivo data showed that tumors with high-level CDC25B were more sensitive to JQ1 than tumors with lower CDC25B. The combination of JQ1 + a pan CDC25 inhibitor was synergistic in gemcitabine-resistant Panc1.gemR cells that had relatively high levels of CDC25B expression compared to parent cells. Conclusion: The data suggest that CDC25B may be an independent indicator of sensitivity to BET inhibitors and that CDC25B may contribute to gemcitabine insensitivity in this tumor type.

References

• Ref 1: The BET inhibitor sensitivity is associated with the expression level of CDC25B in pancreatic cancer models. Cancer Drug Resist. 2024 Oct 18;7:40.