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Abstract
The transition from vegetative growth to multicellular development represents an evolutionary hallmark linked to an oxidative stress signal and controlled protein degradation. We identified the Sem1 proteasome subunit, which connects stress response and cellular differentiation. The sem1 gene encodes the fungal counterpart of the human Sem1 proteasome lid subunit and is essential for fungal cell differentiation and development. A sem1 deletion strain of the filamentous fungus Aspergillus nidulans is able to grow vegetatively and expresses an elevated degree of 20S proteasomes with multiplied ATP-independent catalytic activity compared to wildtype. Oxidative stress induces increased transcription of the genes sem1 and rpn11 for the proteasomal deubiquitinating enzyme. Sem1 is required for stabilization of the Rpn11 deubiquitinating enzyme, incorporation of the ubiquitin receptor Rpn10 into the 19S regulatory particle and efficient 26S proteasome assembly. Sem1 maintains high cellular NADH levels, controls mitochondria integrity during stress and developmental transition.
Highlights
The 26S proteasome represents the major cytoplasmic and nuclear ubiquitin-dependent protein degradation machinery and is composed of a barrel-like 2.5 MDa 20S proteolytic core particle (CP) capped with one or two 19S regulatory particles (RP)
Defects in the function of the proteasome, which degrades a large fraction of intracellular proteins, result in cancer or neurodegenerative diseases
We showed that Sem1 from a multicellular fungus is required for accurate 26S proteasome assembly and specific activity as prerequisites for mitochondria integrity, oxidative stress response and cell differentiation
Summary
The 26S proteasome represents the major cytoplasmic and nuclear ubiquitin-dependent protein degradation machinery and is composed of a barrel-like 2.5 MDa 20S proteolytic core particle (CP) capped with one or two 19S regulatory particles (RP). Sem was originally identified in Saccharomyces cerevisiae in genetic suppression studies of the exocyst [1] It is a multifunctional and intrinsically disordered protein, associating with several functionally diverse protein complexes where it is supporting assembly without being a subunit of the final active complex itself [2]. This includes the human BRCA2 complex (breast cancer complex) required for homologous recombination, the TREX2 complex (transcription export complex 2) needed for mRNA elongation and nuclear export, or the yeast Csn12-Thp complex involved in RNA splicing [2]
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