title: DNA damage targets PKCη to the nuclear membrane via its C1b domain.
abstract: Translocation to cellular membranes is one of the hallmarks of PKC activation, occurring as a result of the generation of lipid secondary messengers in target membrane compartments. The activation-induced translocation of PKCs and binding to membranes is largely directed by their regulatory domains. We have previously reported that PKCη, a member of the novel subfamily and an epithelial specific isoform, is localized at the cytoplasm and ER/Golgi and is translocated to the plasma membrane and the nuclear envelope upon short-term activation by PMA. Here we show that PKCη is shuttling between the cytoplasm and the nucleus and that upon etoposide induced DNA damage is tethered at the nuclear envelope. Although PKCη expression and its phosphorylation on the hydrophobic motif (Ser675) are increased by etoposide, this phosphorylation is not required for its accumulation at the nuclear envelope. Moreover, we demonstrate that the C1b domain is sufficient for translocation to the nuclear envelope. We further show that, similar to full-length PKCη, the C1b domain could also confer protection against etoposide-induced cell death. Our studies demonstrate translocation of PKCη to the nuclear envelope, and suggest that its spatial regulation could be important for its cellular functions including effects on cell death.
authors.affiliation: The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences and The Cancer Research Center, Ben Gurion University of the Negev, Beer Sheva 84105, Israel.
authors.forename: Ana
authors.initials: A
authors.lastname: Tamarkin
authors.forename: Udi
authors.initials: U
authors.lastname: Zurgil
authors.forename: Alex
authors.initials: A
authors.lastname: Braiman
authors.forename: Naama
authors.initials: N
authors.lastname: Hai
authors.forename: Ella
authors.initials: E
authors.lastname: Krasnitsky
authors.forename: Adva
authors.initials: A
authors.lastname: Maissel
authors.forename: Assaf
authors.initials: A
authors.lastname: Ben-Ari
authors.forename: Liat
authors.initials: L
authors.lastname: Yankelovich
authors.forename: Etta
authors.initials: E
authors.lastname: Livneh
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism*; D019556:COS Cells; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism*; D004249:DNA Damage; D005047:Etoposide / Q000494:pharmacology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D009685:Nuclear Envelope / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000235:genetics* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D013347:Subcellular Fractions
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D051745:Protein Kinase C-delta