Parkin Regulates the Activity of Pyruvate Kinase M2

Liu, Kun; Li, Fangzhou; Han, Hai‐Chao; Chen, Yue; Mao, Zebin; Luo, Jianyuan; Zhao, Yingming; Zheng, Bin; Gu, Wei; Zhao, Wenhui

doi:10.1074/jbc.m115.703066

Cited by 94 publications

(68 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PKM plays an important role in the maintenance of different forms of persistent long-term synaptic plasticity [51]. It has been reported that pyruvate kinase M is the substrate of Parkin, a ubiquitin E3 ligase mutated in autosomal recessive, early onset Parkinson’s disease [52]. We detected higher levels (2.2-fold) of PKM in AD patients using five peptides for targeted analysis (Figure 3E, F).…”

Section: Resultsmentioning

confidence: 64%

Quantitative Proteomic Profiling of Cerebrospinal Fluid to Identify Candidate Biomarkers for Alzheimer's Disease

Sathe

Renuse

et al. 2019

Proteomics Clinical Apps

107

View full text Add to dashboard Cite

Purpose Development of novel biomarkers for AD is important for early diagnosis, monitoring disease progression and therapeutic response. The aim of this study was to identify the potential CSF biomarkers for Alzheimer's disease (AD) and evaluate these markers on independent CSF samples using a parallel reaction monitoring mass spectrometry (PRM-MS) assay. Experimental design In this study, we employed high-resolution mass spectrometry and tandem mass tag (TMT) multiplexing technology to identify proteins that might serve as candidate biomarkers for Alzheimer’s disease. Identified potential biomarkers were validated using a parallel reaction monitoring mass spectrometry (PRM-MS) assay. Results We identified 2,327 proteins in the cerebrospinal fluid (CSF) of which 139 were observed to be significantly different in their abundance in the CSF of AD patients versus controls. The proteins whose abundance was altered in AD included a number of known AD marker proteins such as MAPT, NPTX2, SCG2, VGF, GFAP, SST and NCAM1 as well as novel biomarkers such as GSN, PKM and YWHAG. We then sought to validate these findings in a separate set of CSF specimens from AD dementia patients and controls. For the AD group, significant increases were found for YWHAG and PKM, and a significant decrease was observed for VGF by multiplexed targeted parallel reaction monitoring (PRM) experiments. NPTX2 in combination with PKM or with YWHAG led to the best results with AUCs of 0.935 and 0.933, respectively. Conclusions and clinical relevance The identified altered CSF proteins in AD CSF samples will be useful to understand AD pathogenesis.

show abstract

Section: Resultsmentioning

confidence: 64%

Quantitative Proteomic Profiling of Cerebrospinal Fluid to Identify Candidate Biomarkers for Alzheimer's Disease

Sathe

Renuse

et al. 2019

Proteomics Clinical Apps

107

View full text Add to dashboard Cite

show abstract

“…and ubiquitylating pyruvate kinase M2 (PKM2) (162), decreasing its activity and glucose metabolic rate (131). Alterations in ER-mitochondria contact sites: the case of AD.…”

Section: Possible Mechanism Of Oxphos Deficiency In Neurodegenerativementioning

confidence: 99%

Mitochondria, OxPhos, and neurodegeneration: cells are not just running out of gas

Area‐Gómez¹,

Guardia‐Laguarta²,

Schon

et al. 2019

Journal of Clinical Investigation

132

View full text Add to dashboard Cite

“…The interaction between PKM2 and Parkin was favored by glucose starvation. Parkin silencing rescued the activity of PK and supported tumor growth ( 65 ). In addition, the laforin/malin E3-ubiquitin ligase complex, which is mutated in neurodegenerative Lafora disease, interacts and polyubiquitinates both M-isoforms of PK.…”

Section: Ubiquitination and Sumoylationmentioning

confidence: 99%

Posttranslational Modifications of Pyruvate Kinase M2: Tweaks that Benefit Cancer

et al. 2018

View full text Add to dashboard Cite

Cancer cells rewire metabolism to meet biosynthetic and energetic demands. The characteristic increase in glycolysis, i.e., Warburg effect, now considered as a hallmark, supports cancer in various ways. To attain such metabolic reshuffle, cancer cells preferentially re-express the M2 isoform of pyruvate kinase (PKM2, M2-PK) and alter its quaternary structure to generate less-active PKM2 dimers. The relatively inactive dimers cause the accumulation of glycolytic intermediates that are redirected into anabolic pathways. In addition, dimeric PKM2 also benefits cancer cells through various non-glycolytic moonlight functions, such as gene transcription, protein kinase activity, and redox balance. A large body of data have shown that several distinct posttranslation modifications (PTMs) regulate PKM2 in a way that benefits cancer growth, e.g., formation of PKM2 dimers. This review discusses the recent advancements in our understanding of various PTMs and the benefits they impart to the sustenance of cancer. Understanding the PTMs in PKM2 is crucial to assess their therapeutic potential and to design novel anticancer strategies.

show abstract

Parkin Regulates the Activity of Pyruvate Kinase M2

Cited by 94 publications

References 51 publications

Quantitative Proteomic Profiling of Cerebrospinal Fluid to Identify Candidate Biomarkers for Alzheimer's Disease

Quantitative Proteomic Profiling of Cerebrospinal Fluid to Identify Candidate Biomarkers for Alzheimer's Disease

Mitochondria, OxPhos, and neurodegeneration: cells are not just running out of gas

Posttranslational Modifications of Pyruvate Kinase M2: Tweaks that Benefit Cancer

Contact Info

Product

Resources

About