Our lab-profile for this month introduces the work of Professor Arnim Pause, an Associate Professor in the Department of Biochemistry and a Canada Research Chair in Molecular Oncology at McGill University, Canada.
Much of Professor Pause’s early work involved researching eukaryotic translation initiation factors, such as eIF-4A and eIF-4E, which play an important role in protein biosynthesis (Dostie et al., 2000). Concurrent work focussed on the function of VHL, which was discovered to be involved in the ubiquitination of proteins and their degradation by the proteasome (Iwai et al., 1999).
Currently, the Pause lab continues to characterise the function of the VHL protein (Kurban et al., 2008), as well as investigating the role of a His domain-containing protein tyrosine phosphatase encoded by the tumour suppressor gene candidate PTPN23 (Gingras et al., 2009). Professor Pause also studies the role of several proteins in the life cycle of the Hepatitis C virus (Tedbury et al., 2011).
Another major research interest of the Pause lab is the functional characterisation of the FLCN protein. Using mouse models and human cell lines, Hudon et al. (2010) noted that a loss of FLCN expression resulted in both elevated and reduced levels of mTOR signalling, which may account for the differing results observed in previous studies (see here for more information). The Pause lab also collaborated with Dr Andrew Tee’s group at Cardiff University to show that FLCN is associated with HIF signalling (Preston et al., 2011), which has been discussed in more detail in a previous blog post and lab-profile. Further studies have also been planned that make use of a transparent nematode called C. elegans. This multicellular model organism facilitates systematic molecular and genetic approaches, while still maintaining relevance to other eukaryotes such as humans.
To hear more about the research of the Pause lab, and why rare disease research is particularly important for medical research in general, please do watch our video interview (with its accompanying transcript and audio file). Alternatively, join us at the 4th BHD Symposium on 28th – 30th March in Cincinnati, USA. Registration is still open and more information about the patient and family sessions can be found here.
- Dostie J, Ferraiuolo M, Pause A, Adam SA, Sonenberg N. A novel shuttling protein, 4E-T, mediates the nuclear import of the mRNA 5′ cap-binding protein, eIF4E. EMBO J. 2000 Jun 15;19(12):3142-56. PMID: 10856257
- Gingras MC, Zhang YL, Kharitidi D, Barr AJ, Knapp S, Tremblay ML, Pause A. HD-PTP is a catalytically inactive tyrosine phosphatase due to a conserved divergence in its phosphatase domain. PLoS One. 2009;4(4):e5105. Epub 2009 Apr 2. PMID: 19340315
- Hudon V, Sabourin S, Dydensborg AB, Kottis V, Ghazi A, Paquet M, Crosby K, Pomerleau V, Uetani N, Pause A. Renal tumour suppressor function of the Birt-Hogg-Dubé syndrome gene product folliculin. J Med Genet. 2010 Mar;47(3):182-9. Epub 2009 Oct 19. PMID: 19843504
- Iwai K, Yamanaka K, Kamura T, Minato N, Conaway RC, Conaway JW, Klausner RD, Pause A. Identification of the von Hippel-lindau tumor-suppressor protein as part of an active E3 ubiquitin ligase complex. Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12436-41. PMID: 10535940
- Kurban G, Duplan E, Ramlal N, Hudon V, Sado Y, Ninomiya Y, Pause A. Collagen matrix assembly is driven by the interaction of von Hippel-Lindau tumor suppressor protein with hydroxylated collagen IV alpha 2. Oncogene. 2008 Feb 7;27(7):1004-12. Epub 2007 Aug 13. PMID: 17700531
- Preston RS, Philp A, Claessens T, Gijezen L, Dydensborg AB, Dunlop EA, Harper KT, Brinkhuizen T, Menko FH, Davies DM, Land SC, Pause A, Baar K, van Steensel MA, Tee AR. Absence of the Birt-Hogg-Dubé gene product is associated with increased hypoxia-inducible factor transcriptional activity and a loss of metabolic flexibility. Oncogene. 2011 Mar 10;30(10):1159-73. Epub 2010 Nov 8. PMID: 21057536
- Tedbury P, Welbourn S, Pause A, King B, Griffin S, Harris M. The subcellular localization of the hepatitis C virus non-structural protein NS2 is regulated by an ion channel-independent function of the p7 protein. J Gen Virol. 2011 Apr;92(Pt 4):819-30. Epub 2010 Dec 22. PMID: 21177929
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