Marianne Skeie

• Skeie, Marianne; Nikolaysen, Filip; Chitano, Ylenia & Stang, Espen (2020). Hsp90 inhibition and co-incubation with pertuzumab induce internalization and degradation of trastuzumab: Implications for use of T-DM1. Journal of Cellular and Molecular Medicine. ISSN 1582-1838. 24(17), s. 10258–10262. doi: 10.1111/jcmm.15643. Fulltekst i vitenarkiv
• Dietrich, Markus; Malik, Muhammad Salman; Skeie, Marianne; Bertelsen, Vibeke & Stang, Espen (2019). Protein kinase C regulates ErbB3 turnover. Experimental Cell Research. ISSN 0014-4827. 382:111473(2), s. 1–13. doi: 10.1016/j.yexcr.2019.06.018. Fulltekst i vitenarkiv Vis sammendrag

  ErbB3, which belongs to the epidermal growth factor receptor (EGFR) or ErbB family of receptor tyrosine kinases, is involved in progression of several human cancers and a tight regulation of its expression is crucial. An important mechanism for regulation of ErbB proteins is endocytosis and we recently showed that ErbB3, contrary to other ErbB proteins, like EGFR and ErbB2, is constitutively internalized and degraded. Several studies show that protein kinase C (PKC) can regulate the activation, localization and stability of EGFR and ErbB2. Activation of PKC causes their down-regulation from the plasma membrane, but instead of being degraded the receptors accumulate in an endosomal recycling compartment. Since little is known about possible connections between ErbB3 and PKC, we have in the present study investigated effects PKC activity has on ErbB3 stability and intracellular trafficking. While PKC inhibition tends to increase ErbB3 degradation, activation of PKC causes ErbB3 stabilization. The stabilization was not due to inhibited internalization, on the contrary we find that expression of ErbB3 at the plasma membrane is reduced upon PMA-induced PKC activation. However, while endocytosed ErbB3 under normal conditions and upon PKC inhibition is found in early endosomal antigen 1 (EEA1) positive early endosomes and lysosomal-associated membrane protein 1 (LAMP1) positive late endosomes/lysosomes, indicating that it follows the classic degradative pathway, ErbB3 localizes to EEA1 and LAMP1 negative compartments upon PMA-induced activation of PKC. Altogether this shows that PKC regulates the stability of ErbB3, and knockdown experiments show that PKCδ is essential in this process. A likely explanation is that PKC regulates endosomal sorting of ErbB3 and that activated PKC sorts ErbB3 away from the degradative pathway.

• Dietrich, Markus; Malik, Muhammad Salman; Nikolaysen, Filip; Skeie, Marianne & Stang, Espen (2018). Protein kinase C mediated internalization of ErbB2 is independent of clathrin, ubiquitination and Hsp90 dissociation. Experimental Cell Research. ISSN 0014-4827. 371(1), s. 139–150. doi: 10.1016/j.yexcr.2018.08.004. Fulltekst i vitenarkiv Vis sammendrag

  Overexpression of ErbB2 is frequent in cancer and understanding the mechanisms which regulate its expression is important. ErbB2 is considered endocytosis resistant. It has no identified ligand, but upon heterodimerization it is a potent mediator of proliferative signaling. A recent study established a role for protein kinase C (PKC) in internalization and recycling of ErbB2. We have now further investigated the molecular mechanisms involved in PKC-mediated downregulation of ErbB2. We confirm that PMA-induced PKC activation causes ErbB2 internalization, but while the Hsp90 inhibitor 17-AAG induced ErbB2 degradation, PMA had no such effect. When combined with 17-AAG, PMA had additive effect on ErbB2 internalization indicating that Hsp90 inhibition and PKC activation induce internalization by alternative mechanisms. We confirm that while 17-AAG-induced internalization was clathrin-mediated, PMA-induced internalization was clathrin independent. This difference may be explained by while both 17-AAG and PMA reduced the constitutive tyrosine phosphorylation of ErbB2, only 17-AAG induced Hsp90 dissociation, Hsp70 recruitment and ubiquitination of ErbB2. Importantly, since PMA induced internalization of ErbB2, but not dissociation of Hsp90, Hsp90 does not per se retain ErbB2 at the plasma membrane. The morphology of the compartment into which receptors are sorted upon PKC activation has not previously been identified. By immuno-electron microscopy, we show that PMA sorts ErbB2 into a complex tubulovesicular or cisternal organelle resembling a previously described endocytic recycling compartment.

• Fosdahl, Anne Marthe; Dietrich, Markus; Schink, Kay Oliver; Malik, Muhammad Salman; Skeie, Marianne & Bertelsen, Vibeke [Vis alle 7 forfattere av denne artikkelen] (2017). ErbB3 interacts with Hrs and is sorted to lysosomes for degradation. BBA - Molecular Cell Research. ISSN 0167-4889. 1864(12), s. 2241–2252. doi: 10.1016/j.bbamcr.2017.08.011. Fulltekst i vitenarkiv
• Vuong, Tram Thu; Berger, Christian; Bertelsen, Vibeke; Rødland, Marianne Skeie; Stang, Espen & Madshus, Inger Helene (2013). Preubiquitinated chimeric ErbB2 is constitutively endocytosed and subsequently degraded in lysosomes. Experimental Cell Research. ISSN 0014-4827. 319(3), s. 32–45. doi: 10.1016/j.yexcr.2012.10.010. Fulltekst i vitenarkiv
• Hughes, Juliana Bentes; Rødland, Marianne Skeie; Hasmann, Max; Madshus, Inger Helene & Stang, Espen (2012). Pertuzumab Increases 17-AAG-Induced Degradation of ErbB2, and This Effect Is Further Increased by Combining Pertuzumab with Trastuzumab. Pharmaceuticals. 5(7), s. 674–689. doi: 10.3390/ph5070674. Fulltekst i vitenarkiv
• Bertelsen, Vibeke; Sak, Malgorzata Magdalena; Breen, Kamilla; Rødland, Marianne Skeie; Johannessen, Lene Elisabeth & Traub, Linton M. [Vis alle 8 forfattere av denne artikkelen] (2011). A Chimeric Pre-ubiquitinated EGF Receptor is Constitutively Endocytosed in a Clathrin-Dependent, but Kinase-Independent Manner. Traffic: The moving front of cell biology. ISSN 1398-9219. 12(4), s. 507–520. doi: 10.1111/j.1600-0854.2011.01162.x. Fulltekst i vitenarkiv
• Hughes, Juliana Bentes; Berger, Christian; Rødland, Marianne Skeie; Hasmann, Max; Stang, Espen & Madshus, Inger Helene (2009). Pertuzumab increases epidermal growth factor receptor down-regulation by counteracting epidermal growth factor receptor-ErbB2 heterodimerization. Molecular Cancer Therapeutics. ISSN 1535-7163. 8(7), s. 1885–1892. doi: 10.1158/1535-7163.MCT-09-0291. Fulltekst i vitenarkiv
• Kazazic, Maja; Bertelsen, Vibeke; Pedersen, Ketil Winther; Tram, Thu Vuong; Grandal, Michael & Rødland, Marianne Skeie [Vis alle 9 forfattere av denne artikkelen] (2009). Epsin 1 is Involved in Recruitment of Ubiquitinated EGF Receptors into Clathrin-Coated Pits. Traffic: The moving front of cell biology. ISSN 1398-9219. 10(2), s. 235–245. doi: 10.1111/j.1600-0854.2008.00858.x. Fulltekst i vitenarkiv
• Pedersen, Nina Marie; Breen, Kamilla; Rødland, Marianne Skeie; Haslekås, Camilla; Stang, Espen & Madshus, Inger Helene (2009). Expression of Epidermal Growth Factor Receptor or ErbB3 Facilitates Geldanamycin-Induced Down-Regulation of ErbB2. Molecular Cancer Research. ISSN 1541-7786. 7(2), s. 275–284. doi: 10.1158/1541-7786.MCR-07-2183. Fulltekst i vitenarkiv
• Grøvdal, Lene Melsæther; Johannessen, Lene Elisabeth; Rødland, Marianne Skeie; Madshus, Inger Helene & Stang, Espen (2008). Dysregulation of Ack1 inhibits down-regulation of the EGF receptor. Experimental Cell Research. ISSN 0014-4827. 314. doi: 10.1016/j.yexcr.2007.12.017. Fulltekst i vitenarkiv
• Lindbäck, Toril; Fagerlund, Annette; Rødland, Marianne Skeie & Granum, Per Einar (2004). Characterization of the Bacillus cereus Nhe enterotoxin. Microbiology (Reading). ISSN 1350-0872. 150, s. 3959–3967. Fulltekst i vitenarkiv
• Borge, Grethe Iren Andersen; Rødland, Marianne Skeie; Sørhaug, Terje; Langsrud, Thor & Granum, Per Einar (2001). Growth and toxin profiles of Bacillus cereus isolated from different food sources. International journal of food microbiology. ISSN 0168-1605. 69(3), s. 237–246. Fulltekst i vitenarkiv Vis sammendrag

  Eleven strains of Bacillus cereus isolated from milk and meat products have been used to study growth and sporulation profiles in detail. Polymerase chain reaction (PCR) using primers detecting cold shock protein A gene signatures (cspA), showed that none of the strains were the newly suggested species in the B. cereus group, Bacillus weihenstephanensis, comprising psychrotolerant 'cereus' strains, although one of the strains grew at 4°C, two at 6°C and seven grew at 7°C. One of the two strains that grew at 6°C had a maximum growth temperature of 42°C, while the remaining ten strains all grew at temperature of 43°C or higher. Only three strains grew at 48°C. At 42°C the generation time varied between 11 and 34 minutes. Spore germination was much faster for the two strains that grew at 6°C than for the other nine strains in milk at 7 and 10°C. All strains were cytotoxic and contained the non-haemolytic enterotoxin gene (nhe), ten strains contained the enterotoxin T gene (bceT), and only six had the gene (hbl) encoding haemolytic enterotoxin. Two strains showed some microheterogeneity in the nhe operon, but contained all three genes. We can conclude that true B. cereus strains can have growth profiles as expected for B. weihenstephanensis, and that nhe and bceT were not correlated with growth profiles. However, the two psychrotolerant strains with minimal growth temperature of 4 and 6°C, did not contain hbl, as judged from our PCR results.

• Eijsink, Vincent; Rødland, Marianne Skeie; Middelhoven, PH; Brurberg, May-Bente & Nes, Ingolf F. (1998). Comparative studies of class IIa bacteriocins of lactic acid bacteria. Applied Microbiology and Biotechnology. ISSN 0175-7598. 64(9), s. 3275–3281. Fulltekst i vitenarkiv

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