The regulation of protein synthesis and protein folding is crucial for normal cell function. The endoplasmic reticulum (ER) has crucial roles in safeguarding the correct folding and assembling of proteins through the use of ER molecular chaperones. Homeostasis disruption of the ER leads to activation of the Unfolded Protein Response. The UPR is a three-arm pathway that plays a role in regulating ER stress and ultimately leads to cell survival or cell death if the cell fails to recover. There are three major proteins for sensing Endoplasmic Reticulum stress: RNA dependent protein kinase RNA like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring ER-to-nucleus signal kinase 1 (IRE1). PERK activation leads to the phosphorylation of the α-subunit of the translation initiation factor eIF2α on Serine 51 in activating its function. EIF2α phosphorylation leads to up-regulation of GADD34 and GADD34 bind protein phosphatase 1 (PP1) to dephosphorylate eIF2α and brings the cell back into homeostasis. CReP, similar to GADD34, binds to PP1, to dephosphorylate eIF2α. The RVxF motif, RARA sequence, and amino acids throughout the GADD34 sequence play a role in PP1 binding and are essential for dephosphorylating eIF2α in cells. The first 180 amino acids of GADD34 play a role in subcellular localization whereas the first 300 amino acids of CReP play a role for localization to the ER. Early on in the UPR the levels of binding immunoglobulin protein (BiP), CHOP, GADD34, and CReP increase; however, the mRNA levels of CReP drop during the 24-HR Thapsigargin treated stage. Two primary proteins that bind CReP were COPS5 and SNAPIN. Understanding the UPR is important because the inhibiting of GADD34 and CReP have been shown to improve many neurodegenerative diseases.
","abstract_html":"<p>The regulation of protein synthesis and protein folding is crucial for normal cell function. The endoplasmic reticulum (ER) has crucial roles in safeguarding the correct folding and assembling of proteins through the use of ER molecular chaperones. Homeostasis disruption of the ER leads to activation of the Unfolded Protein Response. The UPR is a three-arm pathway that plays a role in regulating ER stress and ultimately leads to cell survival or cell death if the cell fails to recover. There are three major proteins for sensing Endoplasmic Reticulum stress: RNA dependent protein kinase RNA like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring ER-to-nucleus signal kinase 1 (IRE1). PERK activation leads to the phosphorylation of the α-subunit of the translation initiation factor eIF2α on Serine 51 in activating its function. EIF2α phosphorylation leads to up-regulation of GADD34 and GADD34 bind protein phosphatase 1 (PP1) to dephosphorylate eIF2α and brings the cell back into homeostasis. CReP, similar to GADD34, binds to PP1, to dephosphorylate eIF2α. The RVxF motif, RARA sequence, and amino acids throughout the GADD34 sequence play a role in PP1 binding and are essential for dephosphorylating eIF2α in cells. The first 180 amino acids of GADD34 play a role in subcellular localization whereas the first 300 amino acids of CReP play a role for localization to the ER. Early on in the UPR the levels of binding immunoglobulin protein (BiP), CHOP, GADD34, and CReP increase; however, the mRNA levels of CReP drop during the 24-HR Thapsigargin treated stage. Two primary proteins that bind CReP were COPS5 and SNAPIN. Understanding the UPR is important because the inhibiting of GADD34 and CReP have been shown to improve many neurodegenerative diseases.</p>","abstract_has_math":false,"creators":["Padda, Rajneet"],"institution":null,"degree_name":"Master of Science (M.S.)","degree_level":"Thesis - Pacific Access Restricted","degree_discipline":"Biological Sciences","degree_department":null,"school":null,"contributors":["Douglas Weiser"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016-01-01T08:00:00Z","date_published":"2016-01-01T08:00:00Z","updated_at":"2026-07-24T05:36:00Z","subjects":["Biology","Biological sciences","Unfolded proteins"],"languages":[],"rights":[],"rights_urls":["http://rightsstatements.org/vocab/InC/1.0/"],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["9781369188219"],"render_values":[{"text":"9781369188219","href":null,"code":true}]}]},"links":{"outbound_url":"https://scholarlycommons.pacific.edu/uop_etds/170","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Douglas Weiser"]},{"key":"dc:creator","label":"Author","values":["Padda, Rajneet"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2018-06-29T09:07:27Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biological Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis - Pacific Access Restricted"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science (M.S.)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biology","Biological sciences","Unfolded proteins"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["http://rightsstatements.org/vocab/InC/1.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["9781369188219","https://scholarlycommons.pacific.edu/uop_etds/170"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The regulation of protein synthesis and protein folding is crucial for normal cell function. The endoplasmic reticulum (ER) has crucial roles in safeguarding the correct folding and assembling of proteins through the use of ER molecular chaperones. Homeostasis disruption of the ER leads to activation of the Unfolded Protein Response. The UPR is a three-arm pathway that plays a role in regulating ER stress and ultimately leads to cell survival or cell death if the cell fails to recover. There are three major proteins for sensing Endoplasmic Reticulum stress: RNA dependent protein kinase RNA like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring ER-to-nucleus signal kinase 1 (IRE1). PERK activation leads to the phosphorylation of the α-subunit of the translation initiation factor eIF2α on Serine 51 in activating its function. EIF2α phosphorylation leads to up-regulation of GADD34 and GADD34 bind protein phosphatase 1 (PP1) to dephosphorylate eIF2α and brings the cell back into homeostasis. CReP, similar to GADD34, binds to PP1, to dephosphorylate eIF2α. The RVxF motif, RARA sequence, and amino acids throughout the GADD34 sequence play a role in PP1 binding and are essential for dephosphorylating eIF2α in cells. The first 180 amino acids of GADD34 play a role in subcellular localization whereas the first 300 amino acids of CReP play a role for localization to the ER. Early on in the UPR the levels of binding immunoglobulin protein (BiP), CHOP, GADD34, and CReP increase; however, the mRNA levels of CReP drop during the 24-HR Thapsigargin treated stage. Two primary proteins that bind CReP were COPS5 and SNAPIN. Understanding the UPR is important because the inhibiting of GADD34 and CReP have been shown to improve many neurodegenerative diseases.
"]},{"key":"dc:source","label":"Dc Source","values":["135"]},{"key":"dc:title","label":"Title","values":["Regulation of the unfolded protein response by GADD34 and CReP"]}]}],"canonical_facts":{"dc:contributor":["Douglas Weiser"],"dc:creator":["Padda, Rajneet"],"dc:date.available":["2018-06-29T09:07:27Z"],"dc:description.abstract":["The regulation of protein synthesis and protein folding is crucial for normal cell function. The endoplasmic reticulum (ER) has crucial roles in safeguarding the correct folding and assembling of proteins through the use of ER molecular chaperones. Homeostasis disruption of the ER leads to activation of the Unfolded Protein Response. The UPR is a three-arm pathway that plays a role in regulating ER stress and ultimately leads to cell survival or cell death if the cell fails to recover. There are three major proteins for sensing Endoplasmic Reticulum stress: RNA dependent protein kinase RNA like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring ER-to-nucleus signal kinase 1 (IRE1). PERK activation leads to the phosphorylation of the α-subunit of the translation initiation factor eIF2α on Serine 51 in activating its function. EIF2α phosphorylation leads to up-regulation of GADD34 and GADD34 bind protein phosphatase 1 (PP1) to dephosphorylate eIF2α and brings the cell back into homeostasis. CReP, similar to GADD34, binds to PP1, to dephosphorylate eIF2α. The RVxF motif, RARA sequence, and amino acids throughout the GADD34 sequence play a role in PP1 binding and are essential for dephosphorylating eIF2α in cells. The first 180 amino acids of GADD34 play a role in subcellular localization whereas the first 300 amino acids of CReP play a role for localization to the ER. Early on in the UPR the levels of binding immunoglobulin protein (BiP), CHOP, GADD34, and CReP increase; however, the mRNA levels of CReP drop during the 24-HR Thapsigargin treated stage. Two primary proteins that bind CReP were COPS5 and SNAPIN. Understanding the UPR is important because the inhibiting of GADD34 and CReP have been shown to improve many neurodegenerative diseases.
"],"dc:identifier":["9781369188219","https://scholarlycommons.pacific.edu/uop_etds/170"],"dc:rights":["http://rightsstatements.org/vocab/InC/1.0/"],"dc:source":["135"],"dc:subject":["Biology","Biological sciences","Unfolded proteins"],"dc:title":["Regulation of the unfolded protein response by GADD34 and CReP"],"thesis:degree_discipline":["Biological Sciences"],"thesis:degree_level":["Thesis - Pacific Access Restricted"],"thesis:degree_name":["Master of Science (M.S.)"]},"updated_at":"2026-07-24T05:36:00Z"}