Cordula Enenkel

Cordula Enenkel

Associate Professor

Address MSB, Room 5306
1 King's College Circle
Toronto, ON M5S 1A8
Lab Enenkel Lab
Lab Phone 416-946-7884
Office Phone 416-978-3843

Cordula Enenkel was born and raised in Stuttgart, Germany. As a graduate student in Dieter H. Wolf’s laboratory at the University of Stuttgart, she worked on two ubiquitous proteases. She discovered the caspase-like activity of the proteasome and the aminopeptidase bleomycin hydrolase. Her PhD work was supported by the Landesgraduiertenförderung Baden-Württemberg. After receiving her PhD in 1993, she joined Günter Blobel’s laboratory at the Howard Hughes Medical Institute of the Rockefeller University in New York where she was supported by the German Research Foundation (DFG) and the Thyssen Foundation. During her post doc from 1994-1997, she investigated the classical nuclear transport pathway using  importin / karyopherin αβ in yeast. Then, she moved to Berlin, Germany, where she worked as a group leader and lecturer in the Institute of Biochemistry of the Humboldt University / Charité headed by Peter-Michael Kloetzel. Here, she discovered the nuclear import pathway of proteasomes and quality control pathways of proteasome assembly. In 2002, she became Privatdozent (Habilitation), was involved in teaching Biochemistry and worked on the regulation of proteasome homeostasis. In 2011, she moved her laboratory to Toronto.

Dr. Enenkel is interested in the dynamics of proteasomes. Proteasomes are mainly nuclear in dividing cells and sequestered into droplet-like organelles in the cytoplasm of quiescent cells. The organization of these proteasome droplets remains a mystery. Since most of our body’s cells are quiescent, it is important to understand the structure of proteasome droplets and their function with regard to the degradation of toxic proteins. Impaired proteasomal degradation of toxic proteins is associated with neurodegenerative diseases such as Alzheimer’s, Huntington’s and Parkinson’s.


Research Lab

In the Enenkel lab we are studying the nuclear export of proteasomes in quiescent cells. In the cytoplasm of quiescent cells proteasomes are sequestered into motile and reversible protein droplets. The structure and function of these protein droplets is one of the biggest mysteries in cell biology. We use high throughput arrays in the collection of yeast mutants, mass spectrometry, fluorescence microscopy, GFP labelling techniques and methods in cell biology, biochemistry and structural biology to gain insight into the organization of proteasome droplets.

Dr. Enenkel built a network of collaborations with national and international researchers in Israel, US and Germany.


Research Description

Protein Homeostasis in Quiescent Cells

 Figure 1. Proteasome localization. Nuclear proteasomes in dividing yeast and human melanoma cells (left panels). Cytosolic proteasome droplets in quiescent yeast and dendrites of rat neurons (right panel). For review see Enenkel, 2013.

Figure 1. Proteasome localization. Nuclear proteasomes in dividing yeast and human melanoma cells (left panels). Cytosolic proteasome droplets in quiescent yeast and dendrites of rat neurons (right panel). For review see Enenkel, 2013.

The key executor in the turnover of short-lived and unwanted proteins is the proteasome, a conserved protease complex composed of ~ 33 different subunits.  The assembly of these subunits into the proteasome complex is orchestrated by proteasome-dedicated chaperones  (Gu & Enenkel, 2014). The proteasome core particle (CP) harbors the proteolytically active sites. The regulatory particle (RP) is responsible for the recognition of poly-ubiquitylated protein substrates, their unfolding and translocation into the CP. Impaired proteasomal proteolysis results in irreversible and immobile protein aggregates – typical features of neurodegenerative disorders (Enenkel, 2006).

Our current research focuses on the intracellular dynamics of proteasome assemblies – one of the least understood topics in the proteasome field.
Live cell imaging techniques monitoring GFP-labelled proteasomes in proliferating yeast and mammalian cancer cells suggest that proteasomes are primarily nuclear during cell division. In dividing yeast cells, proteasomes are transported by the classical import pathway into the nucleus as inactive precursor complexes suggesting that the nuclear proteasome is assembled in the nucleus (Enenkel, 2014).

Figure 2. Nuclear import of CP precursor complexes (A) and RP modules (B) in dividing yeast cells. (For review see Enenkel, 2014).

Figure 2. Nuclear import of CP precursor complexes (A) and RP modules (B) in dividing yeast cells. (For review see Enenkel, 2014).


In quiescence, mature proteasomes are exported from the nucleus into the cytoplasm and sequestered into motile and reversible droplet-like organelles. The phenomenon of protein droplet formation is not only observed for proteasomes – the second most abundant protein complexes in eukaryotic cells – but also for hundreds of metabolic enzymes suggesting that the cytoplasm is not a homogenous goo but intrinsically structured by multiple droplets (Enenkel, 2014).

How these protein droplets are organized is a mystery in cell biology. My lab aims to understand the organization and function of these enigmatic structures.

Intriguingly, proteasome droplets resolve upon exit from quiescence and mature proteasomes are rapidly imported into the nucleus. We identified Blm10 as a key player in proteasome droplet organization. Blm10 is not only required for proteasome droplet formation but also facilitates nuclear import of mature CP. Blm10 mediates the interaction with nuclear pore proteins and senses the GTPase Ran – the driving force of nuclear transport. Thus, Blm10 represents the first proteasome-dedicated nuclear transport receptor (Weberruss et al., 2013).


Figure 3. Blm10 is involved in the formation of cytosolic proteasome droplets in quiescent yeast cells and facilitates nuclear import of proteasomes upon the resumption of growth.

In our current research we are addressing the following questions:

  •  How are proteasome droplets organized ?
  • Are scaffold proteins required for the formation of proteasome droplets ?
  • Which structures and factors maintain the reversibility and mobility of proteasome droplets ?
  • Are more proteasome-dedicated transport receptors involved in nuclear transport of proteasomes ?
  • What is the function of proteasome droplets with regard to the degradation of toxic proteins ?
  • What is the fate of proteasomes, if they are not sequestered into droplets in quiescence ?
  • Are proteasome droplets proteolytic centres or storage compartments during quiescence ?

Our studies in yeast will foster new ideas relevant to understanding the biology of the quiescent state of human cells in health and disease, and how we can protect cells from accumulating irreversible and immotile proteins aggregates that originate from inefficient degradation of unwanted proteins. We also want to understand, how proteasomes are activated in quiescence to degrade unwanted and toxic proteins like those found in neurodegenerative diseases.

Our work is funded by the Canadian Foundation for Innovation, National Sciences and Engineering Research Council, and Canadian Institutes for Health Research.


View all publications on PubMed

Nuclear Transport of Yeast Proteasomes
Enenkel, C.
Biomolecules (2014) 4, 940-955  Read

Proteasome Assembly
Gu, Z.C. & Enenkel, C.
Cell Mol. Life Sci. (2014) 71, 4729-4745  Read

Proteasome Dynamics
Enenkel, C.
Biochim. Biophys. Acta (2014) 1843, 39-46  Read

Blm10 facilitates nuclear import of proteasome core particles
Weberruss, M.H., Savulescu, A.F., Jando, J., Bissinger, T., Harel, A., Glickman, M.H., Enenkel, C.
EMBO J. (2013) 32, 2697-2707  Read

Nuclear Import of Yeast Proteasomes
Burcoglu, J., Zhao, L. Enenkel, C.
Cells (2015) 4, 387-405  Read