叉頭框蛋白 M1 屬於 forkhead box 家族之一，在細胞週期的進程中扮演重要的角色。透過選擇性剪接的方式，可產生四種不同的同功型叉頭框蛋白 M1，其中只有叉頭框蛋白 M1 b 和 c 是具有轉錄活性。鈣離子是具有多功能的二級信使，介入了細胞內訊息路徑遞並且調控生物性多功能性，包含細胞週期進程、轉錄活性或粒線體代謝等。然而，鈣離子和叉頭框蛋白 M1 之間的關係還尚未了解清楚，我們的研究將使用兩種不同調控鈣離子的相關藥物，分別是鈣離子螯合劑BAPTA-AM 和鈣離子載體 ionomycin，目的是想探討當細胞內鈣離子的濃度改變後，是否會影響轉錄因子叉頭框蛋白 M1 在細胞內的分布以及轉錄活性。首先，我們發現卵巢癌細胞株 BG-1 在缺乏鈣離子情況下，叉頭框蛋白 M1 會分布在細胞核內膜上並且和核纖層蛋白 B 共聚集，這個現象同時也發生在其他癌症及正常細胞株中。此外，我們也證明在鈣離子缺乏下，叉頭框蛋白 M1 和輸出蛋白 1
共聚集在細胞核內膜上且之間的相互作用增加。另一方面，我們也發現當細胞內鈣離濃度出現變化時，類泛素化修飾會影響叉頭框蛋白 M1 在細胞內的分布。此外，鈣離子依賴性的叉頭框蛋白 M1 類泛素化似乎與增加細胞週期 G2/M 的轉變及減少細胞凋亡相關，雖然我們需要更加釐清鈣離子依賴性的叉頭框蛋白 M1泛素化所誘導的特定生物性功能。因此，此研究可以提供鈣離子訊息與叉頭框蛋白 M1 之間分子機制的調控。

The transcription factor forkhead box protein M1 (FOXM1) plays a key role in cell
cycle progression and is a member of the forkhead box family. It has four isoforms
through alternative splicing, but of these isoforms, only FOXM1b and FOXM1c have transcriptional activity. Calcium (Ca2+) is a highly versatile secondary messenger that is involved in the intracellular signaling pathway and regulates several biological functions, including cell cycle progression, transcription factor activation and mitochondria metabolism. However, the relationship between Ca2+ and FOXM1 remains still unclear. We investigated whether intracellular Ca2+ changes affect the location and activity of FOXM1. The Ca2+ chelator BAPTA-AM and the Ca2+ ionophore ionomycin were used to modulate intracellular Ca2+ concentrations. We observed that FOXM1 sequestered to the inner nuclear membrane (INM) and colocalized with nuclear lamin B under Ca2+ depletion in BG-1 ovarian cancer cells as well as in other cancer and normal cell lines. Moreover, FOXM1 colocalized with XPO1 and enhanced their interaction under Ca2+ depletion. However, Ca2+ depletion caused SUMOylation of FOXM1 and its INM localization. In addition, Ca2+-dependent SUMOylated FOXM1 appeared to enhance the G2/M transistion of the cell cycle and decrease cell apoptosis. However, further research is required to elucidate Ca2+-dependent FOXM1 SUMOylation-related biological functions. In conclusion, our findings provide a molecular basis for the relation between Ca2+ signaling and FOXM1 regulation.

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