Johanna M. Brandner and team

Dr. Patrick Zeeuwen, PhD

Laboratory of Skin Biology and Experimental Dermatology
Radboud University Nijmegen Medical Centre
Nijmegen Centre for Molecular Life Sciences
PO Box 9101, 6500 HB Nijmegen
The Netherlands

phone: ++31-24-3617245

NCMLS / Dr. Patrick Zeeuwen

Research focus



A tentative model of the regulatory role of cystatin M/E in processes that control epidermal cornification and desquamation. Human cystatin M/E is an inhibitor of legumain (LGMN), cathepsin L (CTSL) and cathepsin V (CTSV). Inhibition of legumain regulates the processing of (pro)-cathepsins. Inhibition of cathepsin V regulates desquamation, as cathepsin V is able to degrade (corneo)-desmosomal proteins like desmoglein-1, desmocollin-1, and corneodesmosin. Inhibition of human cathepsin L activity by cystatin M/E is thought to be important in the cornification process, as cathepsin L is the elusive processing and activating enzyme for transglutaminase-3 (TGM3). Cathepsin L is also able to process cathepsin D (CTSD), which in turn can activate transglutaminase-1 (TGM1). As cathepsin V is only expressed in humans (pale blue oval), murine cathepsin L probably controls the specific functional enzymatic activities of both human cathepsin L and cathepsin V. Solid lines represent biochemical functions that are known from literature (grey) or deduced from our studies (black). Dashed lines represent unknown functions. BM, basal membrane; SB, stratum basale; SS, stratum spinosum; SG, stratum granulosum; SC, stratum corneum.
Figure from Zeeuwen et al 2010 FASEB J.24:3744-55


Important Publications


last update: 2013, February

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