Martin Rechsteiner

Martin Rechsteiner

Distinguished Professor of Biochemistry

Marty Rechsteiner

B.A. University of California, Berkeley

Ph.D. Johns Hopkins University

Research

References

Marty Rechsteiner's PubMed Literature Search

Research

Besides the RC there are two other proteins that bind the ends of the 20S proteasome and activate peptide hydrolysis.   One is a heptamer of 30K subunits called PA28; the other is a large single polypeptide chain called PA200. We study these two activators as well as a proteasome adaptor called Ecm29 that we propose targets the 26S proteasome to sites of increased proteolysis within eukaryotic cells. Over the past six years, we have cloned and expressed 9 of the RC subunits. We are now using Far Western blotting and in vitro assembly reactions to determine the relative positions of subunits within the RC. Another important goal is to assign functions to each subunit. Six RC subunits belong to a family of ATPases approximately 400 amino acids in length. Although the central regions in the ATPases are highly conserved, the N-terminal and C-terminal sequences are divergent. We have constructed a series of chimeric ATPases to determine whether the divergent regions recognize specific substrates. Several years ago we found that one RC subunit (S5a) binds polyubiquitin chains. We recently discovered that a dimer of two other subunits also binds polyUb chains. We are characterizing the polyUb binding site(s) within these proteins. In addition, we are examining the peptide binding properties of RC subunits because some RC components may bind proteasome extensions to assemble the 26S proteasome and others may bind unfolded regions in proteolytic substrates.

There is a second form of proteasomes. In 1992, we discovered a potent proteasome activator, called REG, that is induced by interferon-* and is thought to play a role in antigen presentation. REG is composed of seven subunits arranged as a ring capable of binding to both ends of the cylindrical proteasome. Our working hypothesis is that REG couples the proteasome to specific cellular structures. We are using 2-hybrid screens and GST-REG chimeras to identify such components.

References

  1. Gonciarz-Swiatek M, Rechsteiner M (2006) Proteasomes and antigen presentation: evidence that a KEKE motif does not promote presentation of the class I epitope SIINFEKL.  Mol Immunol 43:1993-2001
  2. Bett JS, Goellner GM, Woodman B, Pratt G, Rechsteiner M, Bates GP, (2006) Proteasome impairment does not contribute to pathogenesis in R6/2 Huntington’s disease mice: exclusion of proteasome activator REGgamma as a therapeutic target.  Hum Mol Genet 15(1):33-44
  3. Rechsteiner M (2005) The 26S Proteasome. In Protein Degradation, J. Mayer, A. Ciechanover and M. Rechsteiner Eds.   Wiley, Berliin
  4. Ortega J, Heymann JB, Kajava AV, Ustrell V, Rechsteiner M, Steven AC (2005) The axial channel of the 20S proteasome opens upon binding of the PA200 activator.   J Mol Biol. 346:1221-7
  5. Rechsteiner M, Hill C (2005) Mobilizing the proteolytic machine: cell biological roles of proteasome activators and inhibitors.   Trends Cell Biol. 15:27-33
  6. Gorbea C, Goellner GM, Teter K, Holmes RK, Rechsteiner M (2004) Characterization of mammalian Ecm29, a 26 S proteasome-associated protein that localizes to the nucleus and membrane vesicles.   J Biol Chem. 279(52):54849-61
  7. Kajava AV, Gorbea C, Ortega J, Rechsteiner M, Steven AC (2004) New HEAT-like repeat motifs in proteins regulating proteasome structure and function.   J Struct Biol. Jun;146(3):425-30
  8. Ustrell V, Hoffman L, Pratt G, Rechsteiner M (2002) PA200, a nuclear proteasome activator involved in DNA repair. EMBO J 21:3516-25
  9. Li J, et al (2001) Lysine188 substitutions convert the pattern of proteasome activation by REGg to that of REGs a and b. EMBO J 20:3359-3369
  10. Thrower JS, Hoffman L, Rechsteiner M, Pickart CM (2000) Recognition of the polyubiquitin proteolytic signal. EMBO J. 19:94-102

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Last Updated: 3/14/13