the-design-application-inhibiting-peptide-for-rapid-vitro

The Design and Application of Inhibiting Peptide for Rapid <em>In vitro</em> Downregulation of Post-Translational Modifications Levels at a Specific Site

Proteins are the primary executors of life activities and are regulated at transcriptional, translational, and post-translational modification (PTM) ...

The First Affiliated Hospital of Anhui Medical University

 Chronic stress (CS)-induced abnormal metabolism and other subsequent aspects of abnormality are threatening human health. Little is known regarding whether and how protein post-translational-modifications (PTMs) correlate with abnormal metabolism under CS. The aim of this study was to address this issue and also identify novel key protein PTM.  First, we screened which pan-PTM had significant change between control and CS female mice and whether clinical CS females had similar pan-PTM change. Second, we performed quantitative PTM-omics and metabolomics to verify the correlation between abnormal protein PTMs and atypical metabolism. Third, we performed quantitative phospho-omics to identify the key PTM-regulating enzyme and investigate the interaction between PTM protein and PTM-regulating enzyme. Fourth, we attempted to rectify the abnormal metabolism by correcting the activity of the PTM-regulating enzyme. Finally, we examined whether the selected key protein was also correlated with stress scores and atypical metabolism in clinical women.  We initially found that multiple tissues of CS female mice have downregulated pan-crotonylation, and verified that the plasma of clinical CS females also had downregulated pan-crotonylation. Then we determined that ATP5O-K51 crotonylation decreased the most and also caused gross ATP5O decrement, whereas the plasma of CS mice had downregulated phospholipids. Next, downregulating ATP5O crotonylation partially recapitulated the downregulated phospholipid metabolism in CS mice. Next, we verified that HDAC2-S424 phosphorylation determined its decrotonylation activity on ATP5O-K51. Furthermore, correcting HDAC2 hyper-phosphorylation recovered the gross ATP5O level and partially rescued the downregulated phospholipid metabolism in CS mice. Finally, the ATP5O level was also significantly lower and correlated with high stress scores and downregulated phospholipid metabolism in clinical female plasma.  This study discovered a novel PTM mechanism involving two distinct types of PTM in CS and provided a novel reference for the clinical precautions and treatments of CS.

ATP5O Hypo-crotonylation Caused by HDAC2 Hyper-Phosphorylation Is a Primary Detrimental Factor for Downregulated Phospholipid Metabolism under Chronic Stress.

Members of the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing (NLRP) family regulate various physiological and pathological processes. However, none have been shown to regulate actin cap formation or spindle translocation during the asymmetric division of oocyte meiosis I. NLRP4E has been reported as a candidate protein in female fertility, but its function is unknown.

NLRP4E regulates actin cap formation through SRC and CDC42 during oocyte meiosis.

BIN2 inhibition suppress ovarian cancer progression meanwhile protect ovarian function through downregulating HDAC1 and RPS6 phosphorylation respectively.

Article	Year
ATP5O Hypo-crotonylation Caused by HDAC2 Hyper-Phosphorylation Is a Primary Detrimental Factor for Downregulated Phospholipid Metabolism under Chronic Stress. Research (Washington, D.C.)\| PubMed ID: 38645677	2022
NLRP4E regulates actin cap formation through SRC and CDC42 during oocyte meiosis. Cellular & molecular biology letters\| PubMed ID: 38730334	2024
BIN2 inhibition suppress ovarian cancer progression meanwhile protect ovarian function through downregulating HDAC1 and RPS6 phosphorylation respectively. Clinical and translational medicine\| PubMed ID: 39412213	2024

Zhi-Xia Yang

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