Autophagy is an evolutionary conserved process involved in the cellular adaptation to stress and basal levels of autophagy are crucial for cellular metabolism and homeostasis. Cellular recycling by autophagy is characterized by the formation of distinctive double-membrane vesicles (autophagosomes) that engulf unnecessary cytoplasmic components, such as organelles and long-lived proteins. Failure to remove protein aggregates and/or damaged organelles, via autophagy, has been implicated in various medical conditions such as liver disease, neurodegenerative diseases and cancer. Autophagy may suppress or promote cellular proliferation in tumors, depending on the type and metabolic state of the cell, where autophagy is generally believed to mediate these functions cell-autonomously. Here we evaluate the role of BEC-1 and autophagy gene function in cell proliferation, using the C. elegans germ line as an in vivo model. BEC-1 is the C. elegans ortholog of human BECN1/Beclin 1, an essential autophagy regulator and tumor suppressor protein. We show that basal levels of autophagy are required for germline proliferation and that autophagy genes are necessary for the timely progression of the cell cycle. Interestingly, we noticed that autophagy genes may regulate cell proliferation via several pathways. We show that BEC-1/BECN1 acts independently of the GLP-1/Notch or DAF-7/TFG-β pathways, but interacts with components of DAF-2/IIR signaling pathway, to potentiate germline proliferation during development. Moreover, BEC-1/BECN1 requires DAF-18/PTEN but not DAF-16/FOXO for this function and can both promote and inhibit germ cell proliferation depending on the genetic mutant background. Furthermore, ATG-18 and ATG-16.2 also act independently of the GLP-1/Notch and DAF-7/TFG-beta pathways, however it seems that they interact with the canonical of DAF-2/IIR signaling pathway and require DAF-18/PTEN and DAF-16/FOXO for their function. Interestingly, ATG-7 functions together with the DAF-7/TFG-β and independently of the GLP-1/Notch and DAF-2/IIR signaling pathways to promote stem/progenitor cell proliferation. Thus, we conclude that autophagy regulates cellular proliferation in a multifaceted way, probably through interactions with components of at least two non-mutually exclusive signaling pathways: DAF-2/IIR and DAF-7/TFG-β. Our findings indicate that autophagy and BEC-1/BECN1 functions non-cell autonomously, to control germ line proliferation by facilitating cell cycle progression and that BEC-1/BECN1 is probably important for the G2 to M phase transition. Given the evolutionary conservation of autophagy genes from C. elegans to humans, understanding the molecular mechanisms by which autophagy genes modulate the proliferation and/or maintenance of the stem progenitor cell population in vivo may lead to novel autophagy based chemotherapeutic approaches in the future.
","abstract_html":"<p>Autophagy is an evolutionary conserved process involved in the cellular adaptation to stress and basal levels of autophagy are crucial for cellular metabolism and homeostasis. Cellular recycling by autophagy is characterized by the formation of distinctive double-membrane vesicles (autophagosomes) that engulf unnecessary cytoplasmic components, such as organelles and long-lived proteins. Failure to remove protein aggregates and/or damaged organelles, via autophagy, has been implicated in various medical conditions such as liver disease, neurodegenerative diseases and cancer. Autophagy may suppress or promote cellular proliferation in tumors, depending on the type and metabolic state of the cell, where autophagy is generally believed to mediate these functions cell-autonomously. Here we evaluate the role of BEC-1 and autophagy gene function in cell proliferation, using the <em>C. elegans</em> germ line as an <em>in vivo</em> model. BEC-1 is the <em>C. elegans</em> ortholog of human BECN1/Beclin 1, an essential autophagy regulator and tumor suppressor protein. We show that basal levels of autophagy are required for germline proliferation and that autophagy genes are necessary for the timely progression of the cell cycle. Interestingly, we noticed that autophagy genes may regulate cell proliferation via several pathways. We show that BEC-1/BECN1 acts independently of the GLP-1/Notch or DAF-7/TFG-β pathways, but interacts with components of DAF-2/IIR signaling pathway, to potentiate germline proliferation during development. Moreover, BEC-1/BECN1 requires DAF-18/PTEN but not DAF-16/FOXO for this function and can both promote and inhibit germ cell proliferation depending on the genetic mutant background. Furthermore, ATG-18 and ATG-16.2 also act independently of the GLP-1/Notch and DAF-7/TFG-beta pathways, however it seems that they interact with the canonical of DAF-2/IIR signaling pathway and require DAF-18/PTEN and DAF-16/FOXO for their function. Interestingly, ATG-7 functions together with the DAF-7/TFG-β and independently of the GLP-1/Notch and DAF-2/IIR signaling pathways to promote stem/progenitor cell proliferation. Thus, we conclude that autophagy regulates cellular proliferation in a multifaceted way, probably through interactions with components of at least two non-mutually exclusive signaling pathways: DAF-2/IIR and DAF-7/TFG-β. Our findings indicate that autophagy and BEC-1/BECN1 functions non-cell autonomously, to control germ line proliferation by facilitating cell cycle progression and that BEC-1/BECN1 is probably important for the G2 to M phase transition. Given the evolutionary conservation of autophagy genes from <em>C. elegans</em> to humans, understanding the molecular mechanisms by which autophagy genes modulate the proliferation and/or maintenance of the stem progenitor cell population <em>in vivo</em> may lead to novel autophagy based chemotherapeutic approaches in the future.</p>","abstract_has_math":false,"creators":["Ames, Kristina"],"institution":"The Graduate School and University Center of The City University of New York","degree_name":"Doctor of Philosophy","degree_level":"Doctoral","degree_discipline":"Biochemistry","degree_department":null,"school":null,"contributors":[],"advisors":["Alicia Melendez Ph.D","Daniel Weinstein Ph.D"],"committee_chairs":[],"committee_members":["Daniel Weinstein Ph.D","Cathy Savage-Dunn Ph.D","Ana Maria Cuervo, M.D., Ph.D","Iva Greenwald Ph.D"],"year":2016,"date_issued":"2016-02-01T08:00:00Z","date_published":"2016-02-01T08:00:00Z","updated_at":"2026-07-24T01:59:54Z","subjects":["Biology","Cell and Developmental Biology","Genetics","Autophagy","germ cells","C. elegans","BEC-1","Beclin 1","proliferation"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://academicworks.cuny.edu/gc_etds/813","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Alicia Melendez Ph.D","Daniel Weinstein Ph.D"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Daniel Weinstein Ph.D","Cathy Savage-Dunn Ph.D","Ana Maria Cuervo, M.D., Ph.D","Iva Greenwald Ph.D"]},{"key":"dc:creator","label":"Author","values":["Ames, Kristina"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2017-01-05T08:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biochemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The Graduate School and University Center of The City University of New York"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biology","Cell and Developmental Biology","Genetics","Autophagy","germ cells","C. elegans","BEC-1","Beclin 1","proliferation"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://academicworks.cuny.edu/gc_etds/813"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Autophagy is an evolutionary conserved process involved in the cellular adaptation to stress and basal levels of autophagy are crucial for cellular metabolism and homeostasis. Cellular recycling by autophagy is characterized by the formation of distinctive double-membrane vesicles (autophagosomes) that engulf unnecessary cytoplasmic components, such as organelles and long-lived proteins. Failure to remove protein aggregates and/or damaged organelles, via autophagy, has been implicated in various medical conditions such as liver disease, neurodegenerative diseases and cancer. Autophagy may suppress or promote cellular proliferation in tumors, depending on the type and metabolic state of the cell, where autophagy is generally believed to mediate these functions cell-autonomously. Here we evaluate the role of BEC-1 and autophagy gene function in cell proliferation, using the C. elegans germ line as an in vivo model. BEC-1 is the C. elegans ortholog of human BECN1/Beclin 1, an essential autophagy regulator and tumor suppressor protein. We show that basal levels of autophagy are required for germline proliferation and that autophagy genes are necessary for the timely progression of the cell cycle. Interestingly, we noticed that autophagy genes may regulate cell proliferation via several pathways. We show that BEC-1/BECN1 acts independently of the GLP-1/Notch or DAF-7/TFG-β pathways, but interacts with components of DAF-2/IIR signaling pathway, to potentiate germline proliferation during development. Moreover, BEC-1/BECN1 requires DAF-18/PTEN but not DAF-16/FOXO for this function and can both promote and inhibit germ cell proliferation depending on the genetic mutant background. Furthermore, ATG-18 and ATG-16.2 also act independently of the GLP-1/Notch and DAF-7/TFG-beta pathways, however it seems that they interact with the canonical of DAF-2/IIR signaling pathway and require DAF-18/PTEN and DAF-16/FOXO for their function. Interestingly, ATG-7 functions together with the DAF-7/TFG-β and independently of the GLP-1/Notch and DAF-2/IIR signaling pathways to promote stem/progenitor cell proliferation. Thus, we conclude that autophagy regulates cellular proliferation in a multifaceted way, probably through interactions with components of at least two non-mutually exclusive signaling pathways: DAF-2/IIR and DAF-7/TFG-β. Our findings indicate that autophagy and BEC-1/BECN1 functions non-cell autonomously, to control germ line proliferation by facilitating cell cycle progression and that BEC-1/BECN1 is probably important for the G2 to M phase transition. Given the evolutionary conservation of autophagy genes from C. elegans to humans, understanding the molecular mechanisms by which autophagy genes modulate the proliferation and/or maintenance of the stem progenitor cell population in vivo may lead to novel autophagy based chemotherapeutic approaches in the future.
"]},{"key":"dc:title","label":"Title","values":["Role of BEC-1/Beclin 1 and Autophagy Genes in C.elegans Germline Cell Proliferation"]}]}],"canonical_facts":{"dc:contributor.advisor":["Alicia Melendez Ph.D","Daniel Weinstein Ph.D"],"dc:contributor.committeemember":["Daniel Weinstein Ph.D","Cathy Savage-Dunn Ph.D","Ana Maria Cuervo, M.D., Ph.D","Iva Greenwald Ph.D"],"dc:creator":["Ames, Kristina"],"dc:date.available":["2017-01-05T08:00:00Z"],"dc:description.abstract":["Autophagy is an evolutionary conserved process involved in the cellular adaptation to stress and basal levels of autophagy are crucial for cellular metabolism and homeostasis. Cellular recycling by autophagy is characterized by the formation of distinctive double-membrane vesicles (autophagosomes) that engulf unnecessary cytoplasmic components, such as organelles and long-lived proteins. Failure to remove protein aggregates and/or damaged organelles, via autophagy, has been implicated in various medical conditions such as liver disease, neurodegenerative diseases and cancer. Autophagy may suppress or promote cellular proliferation in tumors, depending on the type and metabolic state of the cell, where autophagy is generally believed to mediate these functions cell-autonomously. Here we evaluate the role of BEC-1 and autophagy gene function in cell proliferation, using the C. elegans germ line as an in vivo model. BEC-1 is the C. elegans ortholog of human BECN1/Beclin 1, an essential autophagy regulator and tumor suppressor protein. We show that basal levels of autophagy are required for germline proliferation and that autophagy genes are necessary for the timely progression of the cell cycle. Interestingly, we noticed that autophagy genes may regulate cell proliferation via several pathways. We show that BEC-1/BECN1 acts independently of the GLP-1/Notch or DAF-7/TFG-β pathways, but interacts with components of DAF-2/IIR signaling pathway, to potentiate germline proliferation during development. Moreover, BEC-1/BECN1 requires DAF-18/PTEN but not DAF-16/FOXO for this function and can both promote and inhibit germ cell proliferation depending on the genetic mutant background. Furthermore, ATG-18 and ATG-16.2 also act independently of the GLP-1/Notch and DAF-7/TFG-beta pathways, however it seems that they interact with the canonical of DAF-2/IIR signaling pathway and require DAF-18/PTEN and DAF-16/FOXO for their function. Interestingly, ATG-7 functions together with the DAF-7/TFG-β and independently of the GLP-1/Notch and DAF-2/IIR signaling pathways to promote stem/progenitor cell proliferation. Thus, we conclude that autophagy regulates cellular proliferation in a multifaceted way, probably through interactions with components of at least two non-mutually exclusive signaling pathways: DAF-2/IIR and DAF-7/TFG-β. Our findings indicate that autophagy and BEC-1/BECN1 functions non-cell autonomously, to control germ line proliferation by facilitating cell cycle progression and that BEC-1/BECN1 is probably important for the G2 to M phase transition. Given the evolutionary conservation of autophagy genes from C. elegans to humans, understanding the molecular mechanisms by which autophagy genes modulate the proliferation and/or maintenance of the stem progenitor cell population in vivo may lead to novel autophagy based chemotherapeutic approaches in the future.
"],"dc:identifier":["https://academicworks.cuny.edu/gc_etds/813"],"dc:subject":["Biology","Cell and Developmental Biology","Genetics","Autophagy","germ cells","C. elegans","BEC-1","Beclin 1","proliferation"],"dc:title":["Role of BEC-1/Beclin 1 and Autophagy Genes in C.elegans Germline Cell Proliferation"],"thesis:degree_discipline":["Biochemistry"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Doctor of Philosophy"],"thesis:institution_name":["The Graduate School and University Center of The City University of New York"]},"updated_at":"2026-07-24T01:59:54Z"}