PIM1

Case study 1: Ashley Y Gao, 2022

Cellular senescence is emerging as a driver of idiopathic pulmonary fibrosis (IPF), a progressive and fatal disease with limited effective therapies. The senescence-associated secretory phenotype (SASP), involving the release of inflammatory cytokines and profibrotic growth factors by senescent cells, is thought to be a product of multiple cell types in IPF, including lung fibroblasts. The purpose of this study was to assess the role of Pim-1 kinase as a driver of NF-κB-induced production of inflammatory cytokines from low-passage IPF fibroblast cultures displaying markers of senescence.

The results demonstrate that Pim-1 kinase phosphorylates p65/RelA, activating NF-κB activity and enhancing IL-6 production, which in turn amplifies the expression of PIM1, generating a positive feedback loop. In addition, targeting Pim-1 kinase with a small molecule inhibitor dramatically inhibited the expression of a broad array of cytokines and chemokines in IPF-derived fibroblasts. These findings highlight the therapeutic potential of targeting Pim-1 kinase to reprogram the secretome of senescent fibroblasts and halt IPF progression.

Fig1. Proviral integration site for Moloney murine leukemia virus 1 (Pim-1) regulates phosphorylation and activity of p65/RelA.

Fig2. Proviral Integration site for Moloney murine leukemia virus 1 (Pim-1) promotes lung fibroblast premature senescence.

Case study 2: Yangyang Yuan, 2022

Protein kinase-mediated phosphorylation plays a critical role in many biological processes. However, the identification of key regulatory kinases is still a great challenge. Here, the researchers develop a trans-omics-based method, central kinase inference, to predict potentially key kinases by integrating quantitative transcriptomic and phosphoproteomic data. Using known kinases associated with anti-cancer drug resistance, the accuracy of our method denoted by the area under the curve is 5.2% to 29.5% higher than Kinase-Substrate Enrichment Analysis.

Further experiments reveal that a serine/threonine kinase, PIM1, promotes hepatic conversion and protects human dermal fibroblasts from reprogramming-induced ferroptosis and cell cycle arrest. This study not only reveals new regulatory kinases, but also provides a helpful method that might be extended to predict central kinases involved in other biological processes.

Fig3. Experimental analysis of PIM1 roles in hepatic reprogramming. Immunoblotting of PIM1 in HDFs infected with FHH for the indicated number of days.

Fig4. PAS staining and DiI-ac-LDL uptake assay of HDFs infected with FHH and either PIM1 shRNA or non-targeted shRNA for 12 days.

PIM1 involved in several pathways and played different roles in them. We selected most pathways PIM1 participated on our site, such as Jak-STAT signaling pathway, MicroRNAs in cancer, Acute myeloid leukemia, which may be useful for your reference. Also, other proteins which involved in the same pathway with PIM1 were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

PIM1 has several biochemical functions, for example, ATP binding, manganese ion binding, protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by PIM1 itself. We selected most functions PIM1 had, and list some proteins which have the same functions with PIM1. You can find most of the proteins on our site.

PIM1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with PIM1 here. Most of them are supplied by our site. Hope this information will be useful for your research of PIM1.

RPS19; TFPT; FH; FXR2; NHLH1; BEND7

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