Molecule Information

General Information of the Molecule (ID: Mol04379)

• Name: Cyclin-H (CCNH) ,Homo sapiens
• Synonyms: MO15-associated protein; p34; p37
• Molecule Type: Protein
• Gene Name: CCNH
• Gene ID: 902
• Sequence:
  MYHNSSQKRHWTFSSEEQLARLRADANRKFRCKAVANGKVLPNDPVFLEPHEEMTLCKYY
  EKRLLEFCSVFKPAMPRSVVGTACMYFKRFYLNNSVMEYHPRIIMLTCAFLACKVDEFN
  V SSPQFVGNLRESPLGQEKALEQILEYELLLIQQLNFHLIVHNPYRPFEGFLIDLKTRY
  PI LENPEILRKTADDFLNRIALTDAYLLYTPSQIALTAILSSASRAGITMESYLSESLM
  LKE NRTCLSQLLDIMKSMRNLVKKYEPPRSEEVAVLKQKLERCHSAELALNVITKKRKG
  YEDD DYVSKKSKHEEEEWTDDDLVESL
• Function: Regulates CDK7, the catalytic subunit of the CDK-activatingkinase enzymatic complex. CAK activates the cyclin-associatedkinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. CAKcomplexed to the core-TFIIH basal transcription factor activates RNApolymerase II by serine phosphorylation of the repetitive C-terminaldomain of its large subunit , allowing its escape fromthe promoter and elongation of the transcripts. Involved in cell cyclecontrol and in RNA transcription by RNA polymerase II. Its expressionand activity are constant throughout the cell cycle.{ECO:0000269|PubMed:10024882, ECO:0000269|PubMed:7533895}.
• Uniprot ID: CCNH_HUMAN
• Ensembl ID: ENSG0000013448017
• HGNC ID: HGNC:1594

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

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

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Ovarian cancer [ICD-11: 2C73.0] [1]

• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A2780/DDP cells; Ovarian; Homo sapiens (Human); N.A.
• In Vitro Model: SKOV3/DDP cells; ovarian; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Cell viability assay; Colony formation assay
• Mechanism Description: p37 isoform was implicated in the cancer stem cell-like features of ovarian cancer, as knockdown of AUF1 decreased some cancer stem cell like features, including colony formation, spheroid formation, in vivo tumorigenesis, as well as CD133 expression, in cisplatin-resistant ovarian cancer cells. Importantly, restoration of the p37 isoform enhanced cancer stem cell-like characteristics in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. Consequently, the differential expression of distinct AUF1 isoforms within diverse cellular contexts may underlie its dualistic impact as either a "promoter" or a "suppressor" in cancer. Targeted inhibition of the p37 isoform could potentially offer a viable therapeutic approach for ovarian cancer patients exhibiting elevated AUF1 expression.

References

• Ref 1: Regulation of AUF1 alternative splicing by hnRNPA1 and SRSF2 modulate the sensitivity of ovarian cancer cells to cisplatin. Cell Oncol (Dordr). 2024 Dec;47(6):2349-2366.