Kristina Lindsten, PhD

The Role of Deubiquitylating Enzymes in Human Diseases

Ubiquitylation is a highly controlled posttranslational modification regulating protein stability, activity, or localization. Its function is critical for cellular processes such as signal transduction, cell cycle progression, differentiation, membrane trafficking and apoptosis. Ubiquitylation is a reversible process controlled by the family of deubiquitylating enzymes (DUBs). These enzymes are specialized in removing ubiquitin or ubiquitin-like proteins from substrates and cleaving ubiquitin precursors into functional monomers. To date there are approximately 100 DUBs identified in the human genome but their precise functions and substrate specificity still remain largely unexplored. Several of these DUBs are known to play a direct role in human diseases ranging from neurodegeneration to cancer.

We focus our work on the characterization and identification of the functions of DUBs in various cellular processes. By using an RNAi library we have recently identified the DUB USP4 to be a new player in canonical Wnt-signaling and are presently working on elucidating more of its functions. We have also screened for, and identified, DUBs involved in cellular membrane functions such as endoplasmatic reticulum associated protein degradation (ERAD). We are now exploring the molecular function of these DUBs in cells and their possible role in human diseases.

Photo illustrating the localization of USP19, a transmembrane DUB, to the endoplasmic reticulum (Calnexin) but not to the Golgi (Giantin).

Group members:

  • Mikael Altun, Postdoctoral Researcher
  • Bin Zhao, Graduate Student

Five Selected Publications

Zhao B, Schlesiger C, Masucci MG, Lindsten K.

The Ubiquitin Specific Protease 4  (USP4) is a new player in the Wnt-signaling pathway.

J Cell Mol Med. (2009)

Hassink GC, Zhao B, Sompallae R, Altun M, Gastaldello S, Zinin NV, Masucci MG, Lindsten K.

The ER resident Ubiquitin Specific Protease 19 participates in the UPR and rescues ERAD substrates.

EMBO rep  (2009)

Bosch-Comas A, Lindsten K, Gonzàlez-Duarte R, Masucci MG, Marfany G.

The ubiquitin-specific protease USP25 interacts with three sarcomeric proteins.

Cell Mol Life Sci. 63:723-34 (2006)

Lindsten K, Menéndez-Benito V, Masucci MG, Dantuma NP.

Transgenic Mouse Model of Proteasomal Degradation.

Nature Biotechnol. 21:897-902 (2003)

Lindsten K and Dantuma N.P.

Monitoring the ubiquitin/proteasome system in conformational diseases.

Ageing Res. Rev. 2:433-449 (2003)

Assistant Professor Kristina Lindsten, PhD

Work:
+46 (0) 8 524 87467
E-mail:
Address:
  • Department of Cell and Molecular Biology (CMB)
    Karolinska Institutet
    Box 285
    S-17177 Stockholm Sweden
Last modified by: Kim Andersson 2011-02-24