Disease relevance of RPN4

• Furthermore, heat-induced expression of Rpn4 protein leads to expression of Rpn4 targets at later stages of heat stress, providing a temporal controlling mechanism for proteasome synthesis upon stress conditions that could result in irreversibly damaged proteins [1].

High impact information on RPN4

• Further, we demonstrate that RPN4 is extremely short-lived (t(1/2) approximately 2 min), that it directly interacts with RPN2, a subunit of the 26S proteasome, and that rpn4Delta cells are perturbed in their cell cycle [2].
• The degradation signal of RPN4 was mapped to its N-terminal region, outside the transcription-activation domains of RPN4 [2].
• Regulatory networks revealed by transcriptional profiling of damaged Saccharomyces cerevisiae cells: Rpn4 links base excision repair with proteasomes [3].
• We found that the ubiquitin-dependent degradation of Rpn4 can be mediated by six different lysines [4].
• The biological significance of Ubr2-mediated degradation of Rpn4 is also discussed [5].

Biological context of RPN4

• These data demonstrate that the ubiquitin-proteasome system is controlled by transcriptional regulators of multidrug resistance via RPN4 expression [6].
• We also show that the Yap1p response element is important in the transactivation of RPN4 by Yap1p [6].
• The RPN4 promoter contains an additional sequence that binds Yap1p, a bZIP-type transcription factor that plays an important role in the oxidative stress response and multidrug resistance [6].
• Up-regulation of proteasome genes in response to DNA damage, in contrast, is shown to operate via induction of RPN4 transcription [7].
• The SON1 gene maps to chromosome IV and encodes a nuclear protein of 531 amino acids that contains two acidic stretches and a putative nuclear localization sequence [8].

Associations of RPN4 with chemical compounds

• Indeed, using new chIP-chip experiments we show that predicted interactions for the factors Rpn4p and Pdr1p are observed only after treatment of cells with methyl-methanesulfonate, a DNA-damaging agent [9].

Other interactions of RPN4

• Pdr3p, but not Pdr1p, is required for normal levels of intracellular proteolysis, indicating that the two transcription factors have distinct functions in the control of RPN4 expression [6].
• Two of the five genes thus identified, UFD1 and UFD5, function at post-ubiquitination steps in the UFD pathway [10].
• In these mutants, transcriptional induction of UBI4 was depending in part on the transcription factor Rpn4 [7].
• The role of Rpn4p to function as a transregulator in yeast is corroborated by its ability of stimulating proteasome-associated control element-driven lacZ expression and by experiments using the RPT4 and RPT6 gene promoters coupled to the bacterial cat gene as a reporter [11].
• UFD5 is identical to the previously identified SON1, isolated as an extragenic suppressor of sec63 alleles that impair the transport of proteins into the nucleus [10].

Analytical, diagnostic and therapeutic context of RPN4

• Electrophoretic mobility shift assays using proteasome-associated control element sequences from two regulatory proteasomal genes confirmed specific binding of purified Rpn4p to these sequences [11].
• The FPLC fractions were analyzed by Western blotting using anti-Son1p antibody and antibodies against some authentic subunits of the 26S proteasome, and we found that Son1p co-migrated with components of the 26S proteasome [12].

References