Abstract 3836: Identification of PTPsigma as an autophagic phosphatase
Abstract 3836: Identification of PTPsigma as an autophagic phosphatase
复制标题
摘要 3836：PTPsigma 作为自噬磷酸酶的鉴定
DOI：
--
复制
发表时间：
2011
期刊：
影响因子：
--
通讯作者：
J. MacKeigan
中科院分区：
文献类型：
--
作者：
Katie R. Martin;Yong Xu;B. Looyenga;Ryan J. Davis;Chia;M. Tremblay;H. Xu;J. MacKeigan
会议记录：AACR 2011 年第 102 届年会——2011 年 4 月 2 日至 6 日；佛罗里达州奥兰多
巨自噬是一个动态过程，部分胞质溶胶被封装在双膜囊泡中，并被递送至溶酶体进行降解。 3-磷酸磷脂酰肌醇 (PI(3)P) 集中在自噬囊泡上，并招募对此过程至关重要的效应蛋白。通过 III 类磷脂酰肌醇 3-激酶 (PI3K) Vps34 生产 PI(3)P 已得到充分证实；然而，拮抗自噬这一早期步骤的蛋白磷酸酶仍有待鉴定。为了鉴定此类酶，我们通过 RNA 干扰 (RNAi) 筛选了人类磷酸酶基因，发现 PTPsigma（一种双结构域蛋白酪氨酸磷酸酶 (PTP)）的丢失会增加细胞 PI(3)P。 PTPsigma 缺失导致的丰富的 PI(3)P 阳性囊泡与氨基酸饥饿细胞中观察到的显着相似。因此，我们发现 PTPsigma 的缺失会过度激活组成型和诱导型自噬。最后，我们发现 PTPsigma 定位于细胞中的 PI(3)P 阳性膜，并且这种囊泡定位在自噬过程中得到增强。我们的研究结果提出了 PTPsigma 的新作用，并为自噬的调节提供了见解。这一过程的机制知识对于理解和靶向治疗多种人类疾病至关重要，包括癌症和阿尔茨海默氏病，其中异常自噬可能是病理性的。
引文格式：{作者}。 {摘要标题}[摘要]。见：美国癌症研究协会第 102 届年会记录； 2011年4月2-6日；佛罗里达州奥兰多费城（宾夕法尼亚州）：AACR；癌症研究 2011;71(8 Suppl):摘要 nr 3836.doi:10.1158/1538-7445.AM2011-3836
Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL
Macroautophagy is a dynamic process whereby portions of the cytosol are encapsulated in double-membrane vesicles and delivered to the lysosome for degradation. Phosphatidylinositol-3-phosphate (PI(3)P) is concentrated on autophagic vesicles and recruits effector proteins critical for this process. The production of PI(3)P by the class III phosphatidylinositol 3-kinase (PI3K), Vps34, has been well established; however, protein phosphatases which antagonize this early step in autophagy remain to be identified. To identify such enzymes, we screened human phosphatase genes by RNA interference (RNAi) and found that loss of PTPsigma, a dual-domain protein tyrosine phosphatase (PTP), increases cellular PI(3)P. The abundant PI(3)P-positive vesicles conferred by PTPsigma loss strikingly phenocopied those observed in amino acid-starved cells. Accordingly, we discovered that loss of PTPsigma hyperactivates both constitutive and induced autophagy. Finally, we found that PTPsigma localizes to PI(3)P-positive membranes in cells and this vesicular localization is enhanced during autophagy. Our findings propose a novel role for PTPsigma and provide insight into the regulation of autophagy. Mechanistic knowledge of this process is critical for understanding and targeting therapies for several human diseases, including cancer and Alzheimer's disease, in which abnormal autophagy may be pathological.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3836. doi:10.1158/1538-7445.AM2011-3836