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Ska2/FAM33A: A Novel Gene Implicated in Cell Cycle and Tumorigenesis
Xie Mengyu1,2, Zhang Ying1,2, Zhang Chundong1,2, Bu Youquan1,2*
1Department of Biochemistry and Molecular Biology, ChongQing Medical University, Chongqing 400016, China; 2Molecular Medicine and Cancer Research Center, ChongQing Medical University, Chongqing 400016, China
Abstract: Ska2 (spindle and KT associated 2)， also known as FAM33A (family with sequence similarity 33，
member A)， is a recently identified gene involved in cell cycle regulation and tumorigenesis. It has been demonstrated
that Ska2， along with its coworkers Ska1 and Ska3， constitutes the Ska complex which plays a critical role in the
maintenance of the metaphase plate and/or spindle checkpoint silencing during mitosis. RNAi-mediated Ska2
depletion results into a prolonged checkpoint-dependent delay in a metaphase-like state. Ska2 is over-expressed both
in cancer cell lines and clinical samples including small cell lung cancer and breast cancer. Ska2 regulates both cell
proliferation and tumorigenesis at least by interacting with glucocorticoid receptor. Ska2 overexpression increases
GC transactivation whereas its knockdown decreases transactivation and prevents dexamethasone inhibition of
proliferation. Several classical transcription factors including NF-κΒ and CREB regulate the expression of Ska2
mRNA by directly binding to its promoter. Intriguingly， pre-miRNA-301 is located at the first intron of Ska2 gene， and
the mature miRNA-301 can further regulate Ska2 transcription via targeting the NF-κΒ and ΕΡΚ/CREB pathways，
thus forming positive feed-back loops. Taken together， this novel cell cycle related gene， Ska2， might serve as a novel
target for the diagnosis and treatment of cancers， and thus deserves further investigation.
member A)， is a recently identified gene involved in cell cycle regulation and tumorigenesis. It has been demonstrated
that Ska2， along with its coworkers Ska1 and Ska3， constitutes the Ska complex which plays a critical role in the
maintenance of the metaphase plate and/or spindle checkpoint silencing during mitosis. RNAi-mediated Ska2
depletion results into a prolonged checkpoint-dependent delay in a metaphase-like state. Ska2 is over-expressed both
in cancer cell lines and clinical samples including small cell lung cancer and breast cancer. Ska2 regulates both cell
proliferation and tumorigenesis at least by interacting with glucocorticoid receptor. Ska2 overexpression increases
GC transactivation whereas its knockdown decreases transactivation and prevents dexamethasone inhibition of
proliferation. Several classical transcription factors including NF-κΒ and CREB regulate the expression of Ska2
mRNA by directly binding to its promoter. Intriguingly， pre-miRNA-301 is located at the first intron of Ska2 gene， and
the mature miRNA-301 can further regulate Ska2 transcription via targeting the NF-κΒ and ΕΡΚ/CREB pathways，
thus forming positive feed-back loops. Taken together， this novel cell cycle related gene， Ska2， might serve as a novel
target for the diagnosis and treatment of cancers， and thus deserves further investigation.
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