2016年2月2日 · As a result of SIRT6-mediated deacetylation, PKM2 nuclear protein kinase and transcriptional coactivator functions are abolished. Thus, SIRT6 suppresses PKM2 oncogenic functions, resulting in reduced cell proliferation, migration potential, and invasiveness.

2016年1月19日 · Several previous studies indicate that SIRT6 has tumor-suppressor functions, whereas PKM2 has been reported to promote cell proliferation and tumorigenesis. Based on our characterization of PKM2 as an SIRT6 deacetylase substrate, we examined the role of deacetylase activity in SIRT6 tumor-suppressor functions.

As a result of SIRT6-mediated deacetylation, PKM2 nuclear protein kinase and transcriptional coactivator functions are abolished. Thus, SIRT6 suppresses PKM2 oncogenic functions, resulting in reduced cell proliferation, migration potential, and invasiveness.

SIRT6-dependent deacetylation results in the nuclear export of PKM2 and the suppression of the oncogenic functions of PKM2. In different studies, SIRT6 has been shown to work as a potent tumor suppressor in liver cancer.

2022年6月1日 · These results suggest that SIRT6 deacetylates PKM2 at K433, thereby preventing cancer. The SIRT6-mediated reduction in non-small-cell lung cancer (NSCLC) proliferation is positively correlated with Twist1 expression, which is associated with two distinct tumour processes, metastasis and EMT (Han et al., 2019). In pancreatic ductal ...

2016年1月20日 · SIRT6 has been shown to deacetylate nuclear PKM2, leading to inhibited STAT3 phosphorylation, which disrupted NF-κB-IL-6-STAT3 axis activation, inhibiting the migration of macrophages to...

本研究将为明确SIRT6抑制癌症发生和进展提供分子水平的证据，为治疗PKM2介导的肿瘤性疾病提供药物新靶标和分子靶点。 PKM2是糖代谢途径的一个成员，它将PEP和ADP催化形成pyruvate和ATP，参与糖分解途径（glycoglysis）。 有报道称PKM2可在K433位点发生乙酰化，被乙酰化的PKM2能够影响细胞生长、增殖甚至肿瘤生成。 SIRT6是NAD依赖型的脱乙酰化酶，在多种生理病理事件中都发挥着很重要的作用，比如参与维持染色体稳定性、DNA损伤修复、葡萄 …

2021年2月1日 · In this study, we investigated whether and how SIRT2 deacetylase regulated the protein kinase function of PKM2 in T helper type 17 cell‒mediated inflammatory responses in psoriasis. Sirt2 knockout mice and wild-type littermates had psoriatic dermatitis induced by topical treatment of imiquimod or intradermal injection of recombinant IL-23.

2016年1月19日 · Here we report that SIRT6 binds to and deacetylates nuclear PKM2 (pyruvate kinase M2) at the lysine 433 residue. PKM2 is a glycolytic enzyme with nonmetabolic nuclear oncogenic functions. SIRT6-mediated deacetylation results in PKM2 nuclear export.

2021年1月20日 · SUMOylation of PKM2 lysine 270 (K270) triggered conformation change from tetrameric to dimeric of PKM2, reduced PK activity, and led to nuclear translocation of PKM2. SUMO1 modification of...