Human Sug1/p45 is involved in the proteasome-dependent degradation of Sp1

Kaihong Su, Xiaoyong Yang, Mark D. Roos, Andrew J. Paterson, Jeffrey E. Kudlow

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

The transcription factor Sp1 was previously shown to undergo proteasome-dependent degradation when cells were glucose-starved and stimulated with the adenylate cyclase inducer, forskolin. However, the control of the Sp1 degradation process is largely unknown. Using in vitro and in vivo interaction studies, we show in the present study that Sp1 interacts with human Sug1 [hSug1, also known as p45 or thyroid-hormone-receptor interacting protein ('TRIP1')], an ATPase subunit of the 26 S proteasome and a putative transcriptional modulator. This interaction with Sp1 occurs through the C-terminus of hSug1, the region that contains the conserved ATPase domain in this protein. Both in vitro studies, in reconstituted degradation assays, and in vivo experiments, in which hSug1 is overexpressed in normal rat kidney cells, show that full-length hSug1 is able to stimulate the proteasome-dependent degradation of Sp1. However, hSug1 truncations that lack either the N- or C-terminal domain of hSug1 act as dominant negatives, inhibiting Sp1 degradation in vitro. Also, an ATPase mutant of hSug1, while still able to bind Sp1, acts as a dominant negative, blocking Sp1 degradation both in vitro and in vivo. These results demonstrate that hSug1 is involved in the degradation of Sp1 and that ATP hydrolysis by hSug1 is necessary for this process. Our findings indicate that hSug1 is an exchangeable proteasomal component that plays a critical regulatory role in the proteasome-dependent degradation of Sp1. However, hSug1 is not the factor limiting Sp1 degradation in the cells treated with glucosamine. This and other considerations suggest that hSug1 co-operation with other molecules is necessary to target Sp1 for proteasome degradation.

Original languageEnglish (US)
Pages (from-to)281-289
Number of pages9
JournalBiochemical Journal
Volume348
Issue number2
DOIs
StatePublished - Jun 1 2000

Keywords

  • Diabetes
  • Glucosamine
  • Glycosylation
  • O-GlcNAc
  • Transcription

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Su, K., Yang, X., Roos, M. D., Paterson, A. J., & Kudlow, J. E. (2000). Human Sug1/p45 is involved in the proteasome-dependent degradation of Sp1. Biochemical Journal, 348(2), 281-289. https://doi.org/10.1042/0264-6021:3480281