SKA2/FAM33A: A novel gene implicated in cell cycle, tumorigenesis, and psychiatric disorders

Abstract

SKA2 (spindle and KT associated 2), also referred to as FAM33A (family with sequence similarity 33, member A), is a recently identified gene involved in cell cycle regulation, and growing evidence is implicating its roles in tumorigenesis and psychiatric disorders. 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. SKA2 is over-expressed both in cancer cell lines and clinical samples including small cell lung cancer and breast cancer, whereas downregulation of SKA2 is associated with depression and suicidal ideation. The expression of SKA2 is regulated by transcription factors including NF-κΒ and CREB, miRNAs as well as DNA methylation. In this review, we provide an overview of studies that reveal SKA2 gene and protein characteristics as well as physiological function, with a special focus on its transcription regulatory mechanisms, and also provide a summary regarding the translational opportunity of the SKA2 gene as a clinical biomarker for cancers and psychiatric disorders.

Keywords: Cell cycle; DNA methylation; FAM33A; Gene expression regulation; SKA2; Tumor.

Figure 1

Structure of SKA2 gene. Two splicing variants of SKA2 mRNA and isoforms of protein are shown, introns and exons are represented by straight lines and rectangles, respectively. Dash lines indicates common splicing whereas solid like represents different splicing between two variants.

Figure 2

Regulatory mechanism of SKA2 gene expression. Figure represents a model of bidirectional transcription unit of SKA2 and PRR11 gene. NFY and CREB bind to a promotor region that initiates both SKA2 and PRR11 mRNA transcription. miR-301 regulates NF-κB and ERK/CREB by directly targeting Nkrf and MEOX2, respectively. NF-κB directly regulates transcription of miR-301 and SKA2. CREB directly regulates transcription of SKA2.