| Summary: | 碩士 === 國立陽明大學 === 生化暨分子生物研究所 === 101 === hMMS21 also called Nse2 (non-SMC element 2) is a SUMO E3 ligase. According to the research, MMS21 plays a role in DNA damage repair. Our previous study demonstrated that hMMS21 depletion in MCF7 breast cancer cells reduced E2F1 protein level, and cyclin E-CDK2 activity due to increased p21 expression, and impaired G1-S phase transition of cell cycle. Moreover, our recently study found hMMS21 depletion in HCT116 colorectal cancer cells also increased p21 protein expression.
hMMS21 knockdown in HCT116 cells decreased the cell growth rates. Our results showed that knockdown of MMS21delayed G1-S transition which is probably not associated with elevation of p21 protein expression. Since HCT116 p21-/- cell growth rate was also decreased in hMMS21-knockdowned cells. Both p21 and p27 protein expression levels were elevated in hMMS21-depleted HCT116 cells. In addition, E2F1 and thymidylate synthase (TYMS) protein levels were both decreased in hMMS21-depleted HCT116 cells. And the reduction of TYMS is due to increased protein degradation rate. TYMS is a key enzyme involved in DNA replication in S phase of cell cycle. Our result showed that while knockdown of TYMS in MMS21 depleted HCT116 cells led to DNA damage was not the major crease to reduced cell growth rate. On the other side, knockdown of E2F1 in hMMS21 depleted HCT116 cells recover cell growth rate as normal cells. Taken together, reduced E2F1 expression in MMS21-depleted HCT116 cells seems to be the key role for the decrease cell growth. Knockdown of hMMS21 in HCT116 cells had lower E2F1 levels and ectopic expression of E2F1 could rescue the reduced growth rates.
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