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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Macroautophagy (hereafter referred to as autophagy) is an evolutionarily conserved catabolic process necessary for normal recycling of cellular constituents and for appropriate response to cellular stress. Although several genes belonging to the core molecular machinery involved in autophagosome formation have been discovered, relatively little is known about the nature of signaling networks controlling autophagy upon intracellular or extracellular stimuli. We discovered ATG8-like proteins (MAP1LC3B, GABARAP and GABARAPL1) as novel interactors of MAPK15/ERK8, a MAP kinase involved in cell proliferation and transformation. Based on the role of these proteins in the autophagic process, we demonstrated that MAPK15 is indeed localized to autophagic compartments and increased, in a kinase-dependent fashion, ATG8-like proteins lipidation, autophagosome formation and SQSTM1 degradation, while decreasing LC3B inhibitory phosphorylation. Interestingly, we also identified a conserved LC3-interacting region (LIR) in MAPK15 responsible for its interaction with ATG8-like proteins, for its localization to autophagic structures and, consequently, for stimulation of the formation of these compartments. Furthermore, we reveal that MAPK15 activity was induced in response to serum and amino-acid starvation and that this stimulus, in turn, required endogenous MAPK15 expression to induce the autophagic process. Altogether, these results suggested a new function for MAPK15 as a regulator of autophagy, acting through interaction with ATG8 family proteins. Also, based on the key role of this process in several human diseases, these results supported the use of this MAP kinase as a potential novel therapeutic target.
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PMID:MAPK15/ERK8 stimulates autophagy by interacting with LC3 and GABARAP proteins. 2294 27

Insulin-like signalling is a conserved mechanism that coordinates animal growth and metabolism with nutrient status. In Drosophila, insulin-producing median neurosecretory cells (IPCs) regulate larval growth by secreting insulin-like peptides (dILPs) in a diet-dependent manner. Previous studies have shown that nutrition affects dILP secretion through humoral signals derived from the fat body. Here we uncover a novel mechanism that operates cell autonomously in the IPCs to regulate dILP secretion. We observed that impairment of ribosome biogenesis specifically in the IPCs strongly inhibits dILP secretion, which consequently leads to reduced body size and a delay in larval development. This response is dependent on p53, a known surveillance factor for ribosome biogenesis. A downstream effector of this growth inhibitory response is an atypical MAP kinase ERK7 (ERK8/MAPK15), which is upregulated in the IPCs following impaired ribosome biogenesis as well as starvation. We show that ERK7 is sufficient and essential to inhibit dILP secretion upon impaired ribosome biogenesis, and it acts epistatically to p53. Moreover, we provide evidence that p53 and ERK7 contribute to the inhibition of dILP secretion upon starvation. Thus, we conclude that a cell autonomous ribosome surveillance response, which leads to upregulation of ERK7, inhibits dILP secretion to impede tissue growth under limiting dietary conditions.
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PMID:p53- and ERK7-dependent ribosome surveillance response regulates Drosophila insulin-like peptide secretion. 2539 88

E. histolytica, a protozoan parasite is the causative agent of amoebiasis in human beings. It exists in two different forms - the motile trophozoite form which undergoes encystation under starvation conditions to form the non-motile, osmotically resistant cyst form. Cellular stresses stimulate several signaling cascades which assist the parasite in counter-attacking such conditions thereby, promoting cell survival. To study the stress-associated pathways activated during encystation, we have used Entamoeba invadens, a reptilian parasite as a model organism because of its ability to undergo encystation under in vitro conditions. In this study, we have identified a stress-responsive MAPK which gets upregulated under different stress conditions, including encystation. Sequence analysis and phylogenetic classification show that the MAPK belongs to the atypical MAPK15 family (henceforth, named EiMAPK15), which does not require an upstream MAPKK for its phosphorylation and activation. The in vitro kinase activity of recombinant EiMAPK15 exhibits its auto-phosphorylation ability. Immunolocalization studies reveal that the protein is mainly cytosolic under normal growing conditions but gets translocated into the nucleus under stress conditions. Knockdown of EiMAPK15 using double-stranded RNA was found to reduce the expression of other encystation-specific genes which in turn, resulted in the decline of the overall encystation efficiency of the cells. Overall, the present work has laid the platform for further characterization of this important MAPK gene in Entamoeba invadens.
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PMID:Identification and functional analysis of a stress-responsive MAPK15 in Entamoeba invadens. 2973 Mar 64

Autophagy, a pathway for bulk protein degradation and removal of damaged organelles, represents one of the major responses of cells to stress, thereby exerting a strict control on their correct functioning. Consequently, this process has been involved in the pathogenesis and therapeutic responses of several human diseases. Mitogen-activated protein (MAP) kinase 15 (MAPK15) is an atypical member of the MAP kinase family that recently emerged as a key modulator of autophagy and, through this, of cell transformation. Still, no information is available about signaling pathways mediating the effect of MAPK15 on this process, nor is it known which phase of autophagosome biogenesis is affected by this MAP kinase. Here, we demonstrate that MAPK15 stimulated 5'-AMP-activated protein kinase-dependent activity of UNC-51-like kinase 1 (ULK1), the only protein kinase among the ATG-related proteins, toward downstream substrates and signaling intermediates. Importantly, MAPK15 directly interacted with the ULK1 complex and mediated ULK1 activation induced by starvation, a classical stimulus for the autophagic process. In turn, ULK1 and its highly homologous protein ULK2 are able to transduce MAPK15 signals stimulating early phases of autophagosomal biogenesis in a multikinase cascade that offers numerous potential targets for future therapeutic intervention in cancer and other autophagy-related human diseases.
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PMID:MAPK15 is part of the ULK complex and controls its activity to regulate early phases of the autophagic process. 3013 41