title: Regulatory crosstalk within the mammalian unfolded protein response.
abstract: Increased demands on the protein folding capacity of the endoplasmic reticulum (ER) trigger the unfolded protein response (UPR). Comprised of a tripartite signaling system, the UPR regulates translation and gene transcription to manifest pro-adaptive and, if necessary, pro-apoptotic outcomes. The three UPR pathways, initiated by activating transcription factor 6, inositol requiring enzyme 1, and protein kinase RNA-activated-like ER kinase (PERK), direct distinct downstream signaling events. However, it is becoming increasingly clear that interplay between the cascades is vital in shaping the UPR. In particular, recent discoveries have revealed that PERK-dependent signals mediate both inter- and intra-pathway regulation within the UPR, underscoring the critical role of the PERK pathway in the cellular response to ER stress.
authors.affiliation: Department of Molecular and Cellular Sciences, College of Osteopathic Medicine, Liberty University, 1971 University Boulevard, Lynchburg, VA, 24515, USA, jwbrewer1@liberty.edu.
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Brewer
mesh_terms: D051702:Activating Transcription Factor 6 / Q000378:metabolism; D000818:Animals; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D004722:Endoribonucleases / Q000378:metabolism; D006801:Humans; D017510:Protein Folding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D015398:Signal Transduction; D051742:Transcription Factor CHOP / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis; D056811:Unfolded Protein Response / Q000502:physiology*; D019892:eIF-2 Kinase / Q000378:metabolism*
chemical_list: C497111:ATF6 protein, human; D051702:Activating Transcription Factor 6; C497249:DDIT3 protein, human; D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D051742:Transcription Factor CHOP; C460640:EIF2AK3 protein, human; C528229:ERN1 protein, human; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; D004722:Endoribonucleases