Mikael Altun Group

Senior researcher

Mikael Altun

Organizational unit: Thomas Helledays group
E-mail: Mikael.Altun@ki.se

Mikael Altun's profile page.


Cellular turnover and trafficking of proteins is critical not only in the development of the nervous system but also in the maintenance and plasticity of neurons in the mature and aging nervous system. Protein degradation, which is a highly selective process, is mainly handled by two cellular proteolytic systems, the ubiquitin-proteasomal system (UPS) and the autophagy-lysosomal pathway (ALP). Impairment of the UPS by mutations has been linked to late-onset neurodegenerative diseases like Parkinson´s disease, and neurodegeneration in the context of normal aging. In particular, mutations found in enzymes with deubiquitylating activity (DUB), such as UCH-L1, USP14 or UCH-L3 were shown to be associated with Parkinson’s Disease (PD) pathogenesis, ataxia, and other neurological disorders, respectively. DUBs are cysteine proteases and to date, more than 90 members of this family have been identified. DUBs are identified by their potential capacity to remove conjugated ubiquitin (Ub) and, thus, are important not only in maintaining the pool of free Ub but also as modulators of Ub-tagging signaling (including functional modification, relocation and destruction of proteins). Although we begin to understand more about DUBs, the precise function of most of the DUBs remains largely unknown.

Though little is known about DUBs in the nervous system, we have identified several DUBs that are deregulated in different neurodegenerative conditions. We investigate if UPS enzymes deregulated in disease play a role in disease progression and thus are potential targets for intervention by small molecule inhibitors.

Latest Publications

A small molecule inhibitor of ubiquitin-specific protease-7 induces apoptosis in multiple myeloma cells and overcomes bortezomib resistance.
Chauhan D, Tian Z, Nicholson B, Kumar K, Zhou B, Carrasco R, et al
Cancer Cell 2012 Sep;22(3):345-58

Detection of ubiquitin-proteasome enzymatic activities in cells: application of activity-based probes to inhibitor development.
Kramer H, Nicholson B, Kessler B, Altun M
Biochim. Biophys. Acta 2012 Nov;1823(11):2029-37

Ubiquitin-specific protease 19 (USP19) regulates hypoxia-inducible factor 1α (HIF-1α) during hypoxia.
Altun M, Zhao B, Velasco K, Liu H, Hassink G, Paschke J, et al
J. Biol. Chem. 2012 Jan;287(3):1962-9

Activity-based chemical proteomics accelerates inhibitor development for deubiquitylating enzymes.
Altun M, Kramer H, Willems L, McDermott J, Leach C, Goldenberg S, et al
Chem. Biol. 2011 Nov;18(11):1401-12

Muscle wasting in aged, sarcopenic rats is associated with enhanced activity of the ubiquitin proteasome pathway.
Altun M, Besche H, Overkleeft H, Piccirillo R, Edelmann M, Kessler B, et al
J. Biol. Chem. 2010 Dec;285(51):39597-608

Research group

Mikael Altun

Assistant Professor

Johan Boström

Master’s Student

Michael Feyder

PhD Student

Carolyn Marks

Post Doc

Daniela Papadia

PhD Student

Petra Sykrova

Post Doc