CELL DIVISION CYCLE-ASSOCIATED PROTEIN 7-LIKE; CDCA7L

Alternative titles; symbols

• CDCA7-LIKE
• R1
• JPO2

HGNC Approved Gene Symbol: CDCA7L

Cytogenetic location: 7p15.3 Genomic coordinates (GRCh38): 7:21,900,898-21,945,898 (from NCBI)

▼ Cloning and Expression
Using 3 SP1 (189906)-binding sites in the MAOA (309850) core promoter to screen a human cDNA library, Chen et al. (2005) cloned CDCA7L, which they called R1. The deduced 454-amino acid protein has a calculated molecular mass of 56 kD. The N-terminal half of CDCA7L has an acidic domain followed by a PEST sequence, and the C-terminal half has a nuclear targeting sequence and a DNA-binding domain. The DNA-binding domain contains 12 conserved cysteines, 8 of which form 4 CxxC zinc finger motifs. CDCA7L also has several putative phosphorylation sites. Northern blot analysis detected a 3.0-kb CDCA7L transcript in whole human brain and in all peripheral tissues and human cell lines examined. Immunohistochemical analysis localized CDCA7L to both nucleus and cytosol.

Using the N-terminal domain of MYC (190080) as bait in a yeast 2-hybrid screen, followed by PCR of a human myeloid leukemia cell line cDNA library, Huang et al. (2005) cloned CDCA7L, which they called JPO2. Huang et al. (2005) identified a central leucine zipper domain in the CDCA7L protein. CDCA7L associated with chromatin, nuclear, and cytoplasmic fractions prepared from human embryonic kidney cells during log-phase growth. Northern blot analysis of murine tissues detected highest Cdca7l expression in prostate, thyroid, thymus, and salivary gland; no expression was detected in total brain. Semiquantitative RT-PCR of human tissues produced similar results. CDCA7L appeared to be differentially expressed in medulloblastomas.

▼ Gene Function
By transfecting CDCA7L and a reporter gene into a human neuroblastoma cell line, Chen et al. (2005) found that CDCA7L inhibited the MAOA promoter and MAOA enzymatic activity, and the degree of inhibition correlated with the level of CDCA7L protein expression. Gel-shift assays confirmed that endogenous CDCA7L interacted with SP1 sites of the MAOA promoter, and chromatin immunoprecipitation assays indicated that CDCA7L bound the MAOA promoter in vivo.

Ou et al. (2006) found that serum starvation-induced apoptosis in cultured human neuronal cell lines increased expression of MAOA, p38 kinase (MAPK14; 600289), and caspase-3 (CASP3; 600636) and reduced expression of BCL2 (151430) and the MAOA transcriptional repressor R1. They determined that MAOA and R1 were downstream of p38 kinase and BCL2, but upstream of CASP3, in the apoptotic signaling pathway. Inhibition of MAOA prevented apoptosis, and serum starvation of cortical brain cells from Maoa-deficient mice resulted in reduced apoptosis compared with wildtype mice. Ou et al. (2006) also found that MAOA and R1 were involved in the MYC-induced proliferative signaling pathway in the presence of serum. Using R1 overexpression, R1 small interfering RNA, and a MAOA inhibitor, they showed that R1 and MAOA acted upstream of cyclin D1 (168461) and E2F1 (189971) in the cell proliferation pathway.

▼ Mapping
By genomic sequence analysis, Huang et al. (2005) mapped the CDCA7L gene to chromosome 7p15.