PLK1 (polo like kinase 1) inhibits MTOR complex 1 and promotes autophagy

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PLK1 (polo like kinase 1) inhibits MTOR complex 1 and promotes autophagy

Mechanistic target of rapamycin complex 1 (MTORC1) and polo like kinase 1 (PLK1) are major drivers of cancer cell growth and proliferation, and inhibitors of both protein kinases are currently being investigated in clinical studies. To date, MTORC1's and PLK1's functions are mostly studied separately, and reports on their mutual crosstalk are scarce. Here, we identify PLK1 as a physical MTORC1 ...

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Polo-like kinase 1 inhibits DNA damage response during mitosis

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Checkpoint kinase 1 (Chk1) is required for mitotic progression through negative regulation of polo-like kinase 1 (Plk1).

Although the essential function of checkpoint kinase 1 (Chk1) in DNA damage response has been well established, the role of Chk1 in normal cell cycle progression is unclear. By using RNAi to specifically deplete Chk1, we determined loss-of-function phenotypes in HeLa cells. A vector-based RNAi approach showed that Chk1 is required for normal cell proliferation and survival, inasmuch as a dramat...

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Computational Design of Targeted Inhibitors of Polo-Like Kinase 1 (Plk1)

Computational design of small molecule putative inhibitors of Polo-like kinase 1 (Plk1) is presented. Plk1, which regulates the cell cycle, is often over expressed in cancers. Down regulation of Plk1 has been shown to inhibit tumor progression. Most kinase inhibitors interact with the ATP binding site on Plk1, which is highly conserved. This makes the development of Plk1-specific inhibitors cha...

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Identification of high affinity polo-like kinase 1 (Plk1) polo-box domain binding peptides using oxime-based diversification.

In an effort to develop improved binding antagonists of the polo-like kinase 1 (Plk1) polo-box domain (PBD), we optimized interactions of the known high affinity 5-mer peptide PLHSpT using oxime-based post solid-phase peptide diversification of the N-terminal Pro residue. This allowed us to achieve up to two orders of magnitude potency enhancement. An X-ray crystal structure of the highest affi...

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ژورنال

عنوان ژورنال: Autophagy

سال: 2017

ISSN: 1554-8627,1554-8635

DOI: 10.1080/15548627.2016.1263781