Molecule Information

General Information of the Molecule (ID: Mol00276)

Name	Cyclin-A2 (CCNA2) ,Homo sapiens
Synonyms	Cyclin-A; Cyclin A; CCN1; CCNA Click to Show/Hide
Molecule Type	Protein
Gene Name	CCNA2
Gene ID	890
Location	chr4:121816444-121823883[-]
Sequence	MLGNSAPGPATREAGSALLALQQTALQEDQENINPEKAAPVQQPRTRAALAVLKSGNPRG LAQQQRPKTRRVAPLKDLPVNDEHVTVPPWKANSKQPAFTIHVDEAEKEAQKKPAESQKI EREDALAFNSAISLPGPRKPLVPLDYPMDGSFESPHTMDMSIILEDEKPVSVNEVPDYHE DIHTYLREMEVKCKPKVGYMKKQPDITNSMRAILVDWLVEVGEEYKLQNETLHLAVNYID RFLSSMSVLRGKLQLVGTAAMLLASKFEEIYPPEVAEFVYITDDTYTKKQVLRMEHLVLK VLTFDLAAPTVNQFLTQYFLHQQPANCKVESLAMFLGELSLIDADPYLKYLPSVIAGAAF HLALYTVTGQSWPESLIRKTGYTLESLKPCLMDLHQTYLKAPQHAQQSIREKYKNSKYHG VSLLNPPETLNL Click to Show/Hide
Function	Cyclin which controls both the G1/S and the G2/M transition phases of the cell cycle. Functions through the formation of specific serine/threonine protein kinase holoenzyme complexes with the cyclin-dependent protein kinases CDK1 or CDK2. The cyclin subunit confers the substrate specificity of these complexes and differentially interacts with and activates CDK1 and CDK2 throughout the cell cycle. Click to Show/Hide
Uniprot ID	CCNA2_HUMAN
Ensembl ID	ENSG00000145386
HGNC ID	HGNC:1578
*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

UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s)

1 drug(s) in total

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Metformin

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Acute lymphocytic leukemia				[1]
Sensitive Disease	Acute lymphocytic leukemia [ICD-11: 2B33.0]			Disease Info
Sensitive Drug	Metformin			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
	LKB1/AMPk signaling pathway		Activation	hsa04152
	mTOR signaling pathway		Inhibition	hsa04150
In Vitro Model	ALL CEM cells	Lymph	Homo sapiens (Human)	CVCL_0207
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	XTT assay
Mechanism Description	In metformin-sensitive cells, autophagy was not induced but rather it blocked proliferation by means of arresting cells in the S and G2/M phases which was associated with the downregulation of cyclin A, cyclin B1, and cdc2, but not that of cyclin E. In 10E1-CEM cells that overexpress Bcl-2 and are drug-resistant, the effect of metformin on proliferation was more pronounced, also inducing the activation of the caspases 3/7 and hence apoptosis.

References

Ref 1	Metformin Induces Cell Cycle Arrest and Apoptosis in Drug-Resistant Leukemia Cells. Leuk Res Treatment. 2015;2015:516460. doi: 10.1155/2015/516460. Epub 2015 Nov 25.