scholarly journals A Novel Inhibitor of Homeodomain Interacting Protein Kinase 2 Mitigates Kidney Fibrosis through Inhibition of the TGF-β1/Smad3 Pathway

2017 ◽  
Vol 28 (7) ◽  
pp. 2133-2143 ◽  
Author(s):  
Ruijie Liu ◽  
Bhaskar Das ◽  
Wenzhen Xiao ◽  
Zhengzhe Li ◽  
Huilin Li ◽  
...  
Nephron ◽  
2021 ◽  
pp. 1-5
Author(s):  
Rie Uni ◽  
Mary E. Choi

Necroptosis is a programmed cell death that is characterized by regulated necrosis resulting in plasma membrane rupture and subsequent release of damage-associated molecular patterns (DAMPs). Receptor-interacting protein kinase 3 (RIPK3) is a key mediator of this pathway. Accumulating evidence supports a critical role of RIPK3 and the necroptosis pathway in various human diseases. In this review, we discuss recent investigations that have uncovered pathogenic roles of RIPK3 in both acute kidney injury (AKI) and kidney fibrosis. RIPK3 promotes kidney tubular injury via a mechanism involving mitochondrial dysfunction. Additionally, extracellular mitochondrial DNA, which is one of the necroptotic DAMPs, released from damaged mitochondria correlates with kidney tubular injury and represents a potential novel biomarker. RIPK3 also induces kidney fibrogenesis through AKT-dependent activation of the metabolic enzyme ATP citrate lyase. Thus, the RIPK3-mediated necroptosis pathway may serve as a promising new therapeutic target in AKI and kidney fibrosis.


2013 ◽  
Vol 55 ◽  
pp. 1-15 ◽  
Author(s):  
Laura E. Gallagher ◽  
Edmond Y.W. Chan

Autophagy is a conserved cellular degradative process important for cellular homoeostasis and survival. An early committal step during the initiation of autophagy requires the actions of a protein kinase called ATG1 (autophagy gene 1). In mammalian cells, ATG1 is represented by ULK1 (uncoordinated-51-like kinase 1), which relies on its essential regulatory cofactors mATG13, FIP200 (focal adhesion kinase family-interacting protein 200 kDa) and ATG101. Much evidence indicates that mTORC1 [mechanistic (also known as mammalian) target of rapamycin complex 1] signals downstream to the ULK1 complex to negatively regulate autophagy. In this chapter, we discuss our understanding on how the mTORC1–ULK1 signalling axis drives the initial steps of autophagy induction. We conclude with a summary of our growing appreciation of the additional cellular pathways that interconnect with the core mTORC1–ULK1 signalling module.


2015 ◽  
Vol 28 (6) ◽  
pp. 727-735 ◽  
Author(s):  
Andrew R. Russell ◽  
Tom Ashfield ◽  
Roger W. Innes

The Pseudomonas syringae effector AvrB triggers a hypersensitive resistance response in Arabidopsis and soybean plants expressing the disease resistance (R) proteins RPM1 and Rpg1b, respectively. In Arabidopsis, AvrB induces RPM1-interacting protein kinase (RIPK) to phosphorylate a disease regulator known as RIN4, which subsequently activates RPM1-mediated defenses. Here, we show that AvrPphB can suppress activation of RPM1 by AvrB and this suppression is correlated with the cleavage of RIPK by AvrPphB. Significantly, AvrPphB does not suppress activation of RPM1 by AvrRpm1, suggesting that RIPK is not required for AvrRpm1-induced modification of RIN4. This observation indicates that AvrB and AvrRpm1 recognition is mediated by different mechanisms in Arabidopsis, despite their recognition being determined by a single R protein. Moreover, AvrB recognition but not AvrRpm1 recognition is suppressed by AvrPphB in soybean, suggesting that AvrB recognition requires a similar molecular mechanism in soybean and Arabidopsis. In support of this, we found that phosphodeficient mutations in the soybean GmRIN4a and GmRIN4b proteins are sufficient to block Rpg1b-mediated hypersensitive response in transient assays in Nicotiana glutinosa. Taken together, our results indicate that AvrB and AvrPphB target a conserved defense signaling pathway in Arabidopsis and soybean that includes RIPK and RIN4.


Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 323
Author(s):  
Sujuan Shi ◽  
Lulu An ◽  
Jingjing Mao ◽  
Oluwaseun Olayemi Aluko ◽  
Zia Ullah ◽  
...  

CBL-interacting protein kinase (CIPK) family is a unique group of serine/threonine protein kinase family identified in plants. Among this family, AtCIPK23 and its homologs in some plants are taken as a notable group for their importance in ions transport and stress responses. However, there are limited reports on their roles in seedling growth and development, especially in Solanaceae plants. In this study, NtCIPK23, a homolog of AtCIPK23 was cloned from Nicotiana tabacum. Expression analysis showed that NtCIPK23 is mainly expressed in the radicle, hypocotyl, and cotyledons of young tobacco seedlings. The transcriptional level of NtCIPK23 changes rapidly and spatiotemporally during seed germination and early seedling growth. To study the biological function of NtCIPK23 at these stages, the overexpressing and CRISPR/Cas9-mediated knock-out (ntcipk23) tobacco lines were generated. Phenotype analysis indicated that knock-out of NtCIPK23 significantly delays seed germination and the appearance of green cotyledon of young tobacco seedling. Overexpression of NtCIPK23 promotes cotyledon expansion and hypocotyl elongation of young tobacco seedlings. The expression of NtCIPK23 in hypocotyl is strongly upregulated by darkness and inhibited under light, suggesting that a regulatory mechanism of light might underlie. Consistently, a more obvious difference in hypocotyl length among different tobacco materials was observed in the dark, compared to that under the light, indicating that the upregulation of NtCIPK23 contributes greatly to the hypocotyl elongation. Taken together, NtCIPK23 not only enhances tobacco seed germination, but also accelerate early seedling growth by promoting cotyledon greening rate, cotyledon expansion and hypocotyl elongation of young tobacco seedlings.


2007 ◽  
Vol 19 (4) ◽  
pp. 723-730 ◽  
Author(s):  
Seena K. Ajit ◽  
Suneela Ramineni ◽  
Wade Edris ◽  
Rachel A. Hunt ◽  
Wah-Tung Hum ◽  
...  

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