Identification of a phylogenetically conserved Sug1 CAD family member that is differentially expressed in the mouse nervous system.
We have isolated a cDNA clone from mouse, m56, that encodes a member of the Conserved ATPase-containing Domain (CAD) protein family. Sequence analysis revealed that m56 is identical to mouse mSug1/FZA-B and shares high homology with human Trip1, moth 18-56, and yeast Sug1. When examined, Sug1-like CAD proteins appear to function in the regulation of the 26S proteasome, as well as associate with members of the steroid/thyroid receptor superfamily and other transcriptional activators. m56 can complement the lethal phenotype of loss of SUG1 in yeast. We have examined the tissue distribution of m56 using Northern and Western blots, in addition to immunocytochemistry and in situ hybridization. While m56 was expressed in all tissues and cells examined, several classes of neurons, most notably in the hippocampus, olfactory bulb, and cerebellum, displayed elevated levels of m56 mRNA and protein. We also examined distribution of RNA polymerase II and 26S proteasome subunit 4 (S4) within the mouse brain by in situ hybridization. While all three genes had similar patterns of expression, there were significant differences among them. In moths, the expression of the Sug1 homolog 18-56 is dramatically up-regulated during programmed cell death. In addition, it has been previously demonstrated that the proteasome plays an essential role in the regulation of apoptosis in mammals. We examined the expression of m56 in mouse during natural and induced cell death in a variety of tissues and found no significant changes in expression. Taken together, the data presented here suggest that while m56 is a highly conserved gene that presumably plays essential but complex roles in basal and developmental processes, it may not represent a rate-limiting step in these processes.
Sun
D
D
Molecular and Cellular Biology Program, University of Massachusetts, Amherst 01003, USA.
Swaffield
J C
JC
Johnston
S A
SA
Milligan
C E
CE
Zoeller
R T
RT
Schwartz
L M
LM
D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001221:Aspartate Carbamoyltransferase / Q000235:genetics*; D001921:Brain / Q000378:metabolism*; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D017124:Conserved Sequence; D003546:Cysteine Endopeptidases / Q000737:chemistry; D004080:Dihydroorotase / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry / Q000235:genetics*; D005810:Multigene Family; D010802:Phylogeny; D046988:Proteasome Endopeptidase Complex; D012319:RNA Polymerase II / Q000235:genetics; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors
D048868:Adaptor Proteins, Signal Transducing; C033626:CAD trifunctional enzyme; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D009097:Multienzyme Complexes; C092282:PSMC5 protein, human; C491455:Psmc5 protein, mouse; C106843:SUG1 protein, mammalian; D014157:Transcription Factors; D001221:Aspartate Carbamoyltransferase; D012319:RNA Polymerase II; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D004080:Dihydroorotase; D000074183:ATPases Associated with Diverse Cellular Activities; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing)