Funksjonell regulering av protein interaksjonsnettverk i frisk og sjuk tilstand

Protein deltek i komplekse nettverk med andre protein eller biomolekyl. Slike nettverk er essensielle for alle biologiske funksjonar og endring av desse kan ofte føre til sjukdom.

Vår gruppe fokuserer særleg på protein-fosfolipid interaksjonsnettverk og analyserer samansetting, regulering og funksjonelle roller til desse.

I tillegg er målet å forstå korleis desse nettverka er omforma i frisk og sjuk tilstand der dei metabolske vegane til fosfolipid er kjent å endre seg (særleg i overvekt, type 2-diabetes og kreft).

MOL222 Eksperimentell molekylærbiologi II

MOL210 Lipidbiokjemi: Frå kjemi til sjukdom (ansvarlig)

MOL200 Metabolisme; reaksjonar, regulering og kompartmentalisering

https://scholar.google.no/citations?user=OaNcqFEAAAAJ&hl=en

M Goris, RG Jacobsen, AE Lewis. 2024. Presence of active AKT in the nucleus upon adipocyte differentiation of 3T3-L1 cells. Micropublication Biology. 10.17912/micropub.biology.001140.

E Bariås, M Jakubec, E Førsund, LV Hjørnevik, AE Lewis, Ø Halskau. 2023. Contrasting the phospholipid profiles of two neoplastic cell lines reveal a high PC: PE ratio for SH-SY5Y cells relative to A431 cells. BBRC 656, 23-29

AJ Edson, RG Jacobsen, AE Lewis. 2023. SAF-A/hnRNP U binds polyphosphoinositides via a lysine rich polybasic motif located in the SAP domain. Micropublication Biology. 10.17912/micropub.biology.000761.

Morovicz AP, Mazloumi Gavgani F, Jacobsen RG, Skuseth Slinning M, Turcu DC, Lewis AE (2022). Phosphoinositide 3-kinase signalling in the nucleolus. Adv Biol Regul. 83:100843. doi: 10.1016/j.jbior.2021.100843. 

Mazloumi Gavgani F, Slinning MS, Morovicz AP, Arnesen VS, Turcu DC, Ninzima S, D'Santos CS, Lewis AE. (2021). Nuclear phosphatidylinositol 3,4,5-trisphosphate interactome uncovers an enrichment in nucleolar proteins. Mol Cell Proteomics. 20:100102. doi: 10.1016/j.mcpro.2021.100102. ALso in bioRxiv

F Mazloumi Gavgani, T Karlsson, IL Tangen, A Papdiné Morovicz, V Smith Arnesen, D C Turcu, C Krakstad, J Guillermet-Guibert and AE Lewis (2021). Nuclear upregulation of PI3K p110β correlates with increased rRNA transcription in endometrial cancer cells. J Cell Sci. 34(3):jcs246090. doi: 10.1242/jcs.246090. also on BioRxiv. DOI:10.1101/2019.12.20.884122

RG Jacobsen, F Mazloumi Gavgani, AJ. Edson, M Goris, A Altanchimeg and AE Lewis (2019) Polyphosphoinositides in the nucleus: Roadmap of their effectors and mechanisms of interaction. Adv. Biological Regulation. 72: 7-21.

F Mazloumi Gavgani, V Smith Arnesen, RG Jacobsen, C Krakstad, EA Hoivik, AE Lewis (2018). Class I Phosphoinositide 3-Kinase PIK3CA/p110α and PIK3CB/p110β Isoforms in Endometrial Cancer. Int J Mol Sci. 19(12). pii: E3931. doi: 10.3390/ijms19123931.

T Karlsson, C Krakstad, IL Tangen, EA Hoivik, PM Pollock, HB Salvesen & AE Lewis (2017). Endometrial cancer cells exhibit high expression of p110b and variable response to both p110a and p110b inhibition on PI3K signalling, cell survival and proliferation. Oncotarget. 8:3881-94.

Mjos S, Werner HMJ, Birkeland E, Holst F, Berg A, Halle MK, Tangen IL, Kusonmano K, Mauland KK, Oyan AM, Kalland KH, Lewis AE, Mills GB, Krakstad C, Trovik J, Salvesen HB, Hoivik EA (2017). PIK3CA exon9 mutations associate with reduced survival, and are highly concordant between matching primary tumors and metastases in endometrial cancer. Sci. Reports. 7(1):10240. doi: 10.1038/s41598-017-10717-z.

Jacobsen RM, Gavgani FM, Mellgren G and AE Lewis (2016). DNA Topoisomerase IIa contributes to the early steps of adipogenesis in 3T3-L1 cells. Cellular Signalling. 28:1593-1603.

T Karlsson, A Altanchimeg, O Dobrovolska, DC Turcu and AE Lewis (2016). A polybasic motif in ErbB3-Binding-Protein 1 (EBP1) has key functions in nucleolar localisation and polyphosphoinositide interaction. Biochemical Journal. 473: 2033-47. DOI: 10.1042/BCJ20160274.

AE Lewis, R Aesoy and M Bakke. (2016). Role of EPAC in cAMP-mediated actions in adrenocortical cells. Frontiers in Endocrinology, Neuroendocrine Science. Invited Mini-Review. doi 10.3389/fendo.2016.00063.

CS D’Santos and AE. Lewis (2012). Functional Proteomics: Mapping Lipid-Protein Interactomes. Book Chapter. Integrative Proteomics, Hon-Chiu Eastwood Leung (Ed.), ISBN: 978-953-51-0070-6, InTech, Available from: http://www.intechopen.com/articles/show/title/functional-proteomics-mapping-lipid-protein-interactomes

AE Lewis, L Sommer, MØ Arntzen, Y Strahm, NA Morrice, N Divecha and CS D’Santos (2011). Identification of nuclear phosphatidylinositol 4,5-bisphosphate-interacting proteins by neomycin extraction. Molecular & Cellular Proteomics. 10(2):M110.003376. IF: 8.8

L Aumo, M Rusten, G Mellgren, M Bakke and AE Lewis (2010). Functional roles of PKA and EPAC2 in cAMP-mediated actions in adrenocortical cells. Endocrinology. 151:2151-61.IF: 4.94.

VV Ardawatia, M Masià-Balagué, BF Krakstad, BB Johansson, KM Kreitzburg, E Spriet, AE Lewis, TE Meigs, AM Aragay (2010). Gα(12) binds to the N-terminal regulatory domain of p120(ctn), and downregulates p120(ctn) tyrosine phosphorylation induced by Src family kinases via a RhoA independent mechanism. Exp. Cell Res. in press 2010 Oct 22. IF: 3.59

EA Hoivik, AE Lewis, L Aumo and M Bakke (2009). Molecular aspects of steroidogenic factor 1 (SF-1). Review. Molecular Cellular Endocrinology.315:27-39. IF: 3.61.

MØ Arntzen, CL Osland, CR Raa, R Kopperud, SO Døskeland, AE Lewis and CS D’Santos (2009). POSTMan (POST-translational Modification analysis), a software application for PTM discovery. Proteomics. 9:1400-6. IF: 4.59.

Hoivik EA, Aumo L, Aesoy R, Lillefosse H, Lewis AE, Perrett RM, Stallings NR, Hanley NA, Bakke M (2008). Deoxyribonucleic Acid methylation controls cell type-specific expression of steroidogenic factor 1. Endocrinology. 149:5599-609. IF: 4.94.

AE Lewis, M Rusten, EA Hoivik, EL Vikse, ML Hansson, AE Wallberg, and M Bakke (2008). Phosphorylation of Steroidogenic Factor 1 Is Mediated by Cyclin-Dependent Kinase 7. Molecular Endocrinology. 22: 91–104. IF: 5.39.

AJ Fikaris,AE Lewis, A Abulaiti, O Tsygankova and JL Meinkoth (2006). Ras triggers ATR activation and apoptosis through sustained mitogenic signaling. J. Biol. Chem. 281:34759-67. IF: 5.52.

AE Lewis, AJ Fikaris, G Prendergast and JL Meinkoth. (2004). TSH and serum regulate thyroid cell proliferation through differential effects on p27 expression and localization. Molecular Endocrinology. 18: 2321-2332. IF: 5.39.

AE Lewis, BCY Wong, MJS Langman and MC Eggo. (2004). Protein kinase C delta is not activated by caspase-3 and its inhibition is sufficient to induce apoptosis in the colon cancer line, COLO 205. Cellular Signalling. 17: 253-262. IF: 4.3.

G Cheng, AE Lewis and JL Meinkoth. (2003). Ras stimulates aberrant cell cycle progression and apoptosis in rat thyroid cells. Molecular Endocrinology. 17: 450-459. IF: 5.39.

AE Lewis, BCY Wong, MJS Langman and MC Eggo. (2003). Protein kinase C inhibition induces DNA fragmentation in Colo 205 cells, which is blocked by cysteine protease inhibition but not mediated through caspase-3. Experimental Cell Research. 289: 1-10. IF: 3.95.

Y Qiu, CE Waters, AE Lewis, MJ Langman and MC Eggo. (2002). Oestrogen-induced apoptosis in colonocytes expressing oestrogen receptor b. Journal of Endocrinology. 174: 369-377. IF: 2.79.

S Dearn, M Rahman, A Lewis, Z Ahmed, MC Eggo and AS Ahmed. (2000). Activation of platelet-activating factor (PAF) receptor stimulates nitric oxide (NO) release via protein kinase C-α in HEC-1B human endometrial epithelial cell line. Molecular Medicine. 6: 37-49. IF: 3.41.

2023

• Bariås, Espen; Jakubec, Martin; Førsund, Elise et al. (2023). Contrasting the phospholipid profiles of two neoplastic cell lines reveal a high PC:PE ratio for SH-SY5Y cells relative to A431 cells. (ekstern lenke)
• Edson, Amanda Jayne; Jacobsen, Rhian Gaenor; Lewis, Aurelia Eva (2023). SAF-A/hnRNP U binds polyphosphoinositides via a lysine rich polybasic motif located in the SAP domain. (ekstern lenke)
• Tollaksvik, Thomas; Haugland, Gyri Teien; Lewis, Aurelia Eva (2023). Tailoring mRNA towards future vaccine for lumpfish (Cyclopterus lumpus) – Protein expression and immune responses. (ekstern lenke)
• Haukland, Ida Soo; Haugland, Gyri Teien; Lewis, Aurelia Eva (2023). The road towards mRNA vaccine as a potential therapeutic strategy for Atlantic Salmon (Salmo salar). (ekstern lenke)

2022

• Papdine Morovicz, Andrea; Mazloumi Gavgani, Fatemeh; Jacobsen, Rhian Gaenor et al. (2022). Phosphoinositide 3-kinase signalling in the nucleolus. (ekstern lenke)

2021

• Mazloumi Gavgani, Fatemeh; Karlsson, Thomas; Tangen, Ingvild Løberg et al. (2021). Nuclear upregulation of class I phosphoinositide 3-kinase p110β correlates with high 47S rRNA levels in cancer cells. (ekstern lenke)

Se en full oversikt over publikasjoner i Cristin

Identifying PI interacting nuclear proteins to understand their function:

Using a quantitative proteomic methods to enrich for and identify nuclear phosphoinositide effector proteins. Using this method, we have identified nuclear proteins interacting with phosphatidylinositol (4,5) bisphosphate (PtdIns(4,5)P2) (PubMed ID 21048195) and PtdIns(3,4,5)P3, two of the 7 existing PIs.

Current projects include further analysis of these potential interactions (PubMed ID 27118868)

• Biochemical validation of the interactions
• Role of PtdIns(4,5)P2 and PtdIns(3,4,5)P3 in the function of these proteins
• Mechanism of regulation of these interactions
• Effect of PtdIns(4,5)P2 and PtdIns(3,4,5)P3 on protein structure

 

Mapping changes in protein-phosphoinositide interactomes in pathological states

Our current goal is to map which protein-phosphoinositide networks are remodelled in pathological states where the phosphoinositide metabolic pathways are known to be altered (e.g. obesity, type 2 diabetes mellitus, cancer).

Long term goal: To design small molecules disrupting specific protein-phosphoinositide interactions found to be altered in these diseases.

 

To determine the nuclear role of the PI3K pathway in cancer development