The ubiquitin-proteasome pathway in thymocyte apoptosis: caspase-dependent processing of the deubiquitinating enzyme USP7 (HAUSP)

Mol Immunol. 2002 Nov;39(7-8):431-41. doi: 10.1016/s0161-5890(02)00123-2.


Programmed cell death (apoptosis) is crucial for thymocyte development. We analyzed the role of the ubiquitin (Ub)-proteasome pathway in dexamethasone-triggered and TCR-mediated apoptosis in fetal thymic organ culture (FTOC). Proteasome activity was increased in apoptotic thymocytes, as visualized by active-site labeling of proteasomal beta subunits. The activity of deubiquitinating enzymes in murine apoptotic thymocytes was likewise examined by active-site labeling. We show that the deubiquitinating enzyme USP7 (HAUSP) is proteolytically processed upon dexamethasone-, gamma-irradiation-, and antigen-induced cell death. Such processing of HAUSP does not occur in caspase 3-/- thymocytes, or upon pretreatment of wild type thymocytes with the general caspase inhibitor ZVAD-fmk. Thus, our results suggest that thymocyte apoptosis leads to modification of deubiquitinating enzymes by caspase activity and may provide an additional link between the ubiquitin-proteasome pathway and the caspase cascade during programmed cell death.

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Animals
  • Apoptosis* / drug effects
  • Caspase 12
  • Caspase 3
  • Caspases / physiology*
  • Cysteine Endopeptidases / physiology*
  • Dexamethasone / pharmacology
  • Endopeptidases / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Multienzyme Complexes / physiology*
  • Organ Culture Techniques
  • Proteasome Endopeptidase Complex
  • T-Lymphocytes / physiology*
  • Ubiquitin / metabolism*
  • Ubiquitin Thiolesterase
  • Ubiquitin-Specific Peptidase 7


  • Amino Acid Chloromethyl Ketones
  • Multienzyme Complexes
  • Ubiquitin
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • Dexamethasone
  • Endopeptidases
  • USP7 protein, human
  • Ubiquitin Thiolesterase
  • Ubiquitin-Specific Peptidase 7
  • CASP12 protein, human
  • CASP3 protein, human
  • Casp12 protein, mouse
  • Casp3 protein, mouse
  • Caspase 12
  • Caspase 3
  • Caspases
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex