DUB‐1, a fate determinant of dynein heavy chain in B‐lymphocytes, is regulated by the ubiquitin–proteasome pathway

Abstract Ubiquitinaiton and deubiquitination of post‐translational modification play counter roles in determining the fate of protein function in eukaryotic system for maintaining the cellular homeostasis. Even though novel family members of growth‐regulating deubiquitinating enzymes (DUB‐1 and DUB‐2) have been identified, their target proteins and functions are poorly understood. Dub genes encoding DUB‐1 and DUB‐2 are immediate‐early genes and are induced in response to cytokine stimuli rapidly and transiently. In order to explore the possible proteins regulated by DUB‐1, we performed the matrix assisted laser desorption ionization time‐of‐flight mass spectrometry (MALDI‐TOF‐MS) analysis followed by immunoprecipitation. We confirmed that DUB‐1 interacts with dynein heavy chain, which is known to regulate the movement of organelles and microtubule binding ability. In addition, structural and immunoprecipitation analyses revealed that DUB‐1 contains a putative PEST motif and is polyubiquitinated, indicating that DUB‐1 is also regulated by the ubiquitin–proteasome pathway. J. Cell. Biochem. 105: 1420–1429, 2008. © 2008 Wiley‐Liss, Inc.