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At least 19 recordsLinked to original sources
PubMed1991

Evidence for a particulate location of ubiquitin conjugates and ubiquitin-conjugating enzymes in rabbit brain.

Conjugate ubiquitin was previously found in the nucleus, cytoplasm, and membranes of eukaryotic cells while the enzymes of the ubiquitin-conjugating system appear to be cytoplasmic. We have prepared the mitochondrial fraction from rabbit brain by discontinuous density gradient ultracentrifugation and by Western blotting, using a specific antibody against conjugate ubiquitin, showing that it contains ubiquitin conjugates in a very wide molecular weight range. Electron microscopy and measurement of specific enzyme markers show that this fraction not only contains mitochondria but also some endoplasmic reticulum vesicles. Immunostaining with anti-ubiquitin IgG followed by immunodecoration with colloidal gold particles provides evidence for the presence of conjugate ubiquitin both in mitochondria and in the endoplasmic reticulum. Furthermore, this "mitochondrial fraction" shows a pronounced ATP-dependent ability to conjugate 125I-ubiquitin into a number of endogenous proteins as evidenced by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Addition of E1, E2, and E3, the enzymes of the ubiquitin conjugating system purified from rabbit reticulocytes, does not further increase this ubiquitination nor incorporate 125I-ubiquitin into additional protein bands. The same mitochondrial fraction is not able to carry out any ATP-dependent degradation of 125I-albumin; however, it contains an isopeptidase activity able to release the covalently incorporated 125I-ubiquitin and is also able to conjugate 125I-ubiquitin to exogenous proteins as oxidized RNase. By affinity chromatography on ubiquitin-agarose of fraction II of a crude Triton X-100 extract of the mitochondrial fraction, several proteins corresponding in Mr to the E1 and E2s enzymes were obtained. These proteins were also able to form specific ubiquitin-thiol ester bounds on sodium dodecyl sulfate-polyacrylamide gels and to support 125I-ubiquitin conjugation to oxidized RNase. Detergent fractionation of the mitochondrial fraction provided evidence for a possible localization of the ubiquitin conjugating activity in the mitochondrial external membrane and endoplasmic reticulum. The presence of an active ubiquitin protein conjugating system in mitochondria and endoplasmic reticulum may be related to the turnover of organelle proteins as well as to specific cell functions such as import of proteins into mitochondria and ubiquitination of externally oriented membrane-bound proteins.

Animals↗
PubMed1991

Demonstration of a factor in fraction I of reticulocyte lysates necessary for the steady state accumulation of ubiquitin conjugates of des-75-76-ubiquitin.

Addition of des-75-76-ubiquitin (ubiquitin lacking its two C-terminal glycine residues) to reticulocyte lysates leads to the inhibition of proteolysis and the formation of conjugates between it and native ubiquitin, as demonstrated by the incorporation of both 125I-labeled des-75-76-ubiquitin and 125I-labeled ubiquitin into these conjugates. Conjugate formation is blocked by methylation of the amino groups of des-75-76-ubiquitin, consistent with the concept that the conjugates represent attachment of the ubiquitin alpha-carboxyl group to amino groups of des-75-76-ubiquitin. The lack of significant direct competition for conjugate formation by typical ubiquitinatable proteolysis substrates or by des-73-76-ubiquitin, together with differences in conjugate formation between des-73-76-ubiquitin and des-75-76-ubiquitin demonstrated earlier, indicates that the enzyme involved recognizes the ubiquitin sequence as a substrate for ubiquitination. Increasing concentrations of native ubiquitin first increase and then reduce the steady state level of conjugates of the des-75-76-protein, the inhibitory effects of high concentrations consistent with competition by native ubiquitin for conjugate formation. Upon fractionation of reticulocyte lysates, a factor essential to the net synthesis of conjugates of des-75-76-ubiquitin was demonstrated to be present in Fraction I and to behave as a protein of molecular weight 38,000. The role in this system of a factor from Fraction I other than ubiquitin indicates that a novel pathway is involved.

Animals↗
PubMed1992

Subcellular localization of ubiquitin and ubiquitinated proteins in Arabidopsis thaliana.

Ubiquitin is a highly conserved, 76-amino acid, eukaryotic protein. Its widely accepted role as a proteolytic cofactor depends on its unique ability to covalently ligate to other cellular proteins. While there is good evidence for the existence of such ubiquitinated proteins in the cytosolic and nuclear compartments, relatively little is known about the presence of free ubiquitin and ubiquitinated proteins in other subcellular compartments. This is especially true of higher plants, which have not previously been the subject of extensive biochemical subcellular localizations of ubiquitinated proteins. We extracted cell wall proteins and purified nuclei, vacuoles, chloroplasts, and microsomes from chlorophyllous tissues of Arabidopsis. Immunoblot analyses were used to compare the profiles of ubiquitinated proteins from purified subcellular fractions to those from unfractionated extracts. Purified nuclei contained, in addition to a complex mixture of high molecular mass ubiquitinated proteins, a strongly immunoreactive 28-kDa protein. In the apoplastic extract, we did not detect any ubiquitinated proteins enriched above the background level of those due to cytosolic contamination. Vacuoles appeared to contribute significantly to the ubiquitinated proteins present in the whole protoplast extract. At least three high molecular mass ubiquitinated proteins were unique to the vacuolar extract. Chloroplast stromal proteins did not react specifically with anti-ubiquitin antibodies. When microsomal ubiquitinated proteins were compared to those found in a whole protoplast extract, a distinct pattern was evident. Microsomal ubiquitinated proteins were not visible in the 10,000 x g supernatant used to prepare the 100,000 x g pellet, indicating that they were probably low abundance proteins in the protoplast extract.

Cell Fractionation↗
PubMed1992

Iodination of tyrosine 59 of ubiquitin selectively blocks ubiquitin's acceptor activity in diubiquitin synthesis catalyzed by E2(25K).

Covalent ligation of multiubiquitin chains targets eukaryotic proteins for degradation. Ubiquitin-conjugating enzyme E2(25K) utilizes isolated ubiquitin as the substrate for synthesis of such chains, in which successive ubiquitin units are linked by isopeptide bonds involving the side chain of Lys-48 of one ubiquitin and the COOH group of Gly-76 of the next. During continuous synthesis of multiubiquitin chains in the presence of purified ubiquitin-activating enzyme and E2(25K), there was a slight discrimination against radioiodinated ubiquitin (2.3-fold reduction in specific radioactivity of diubiquitin relative to value expected for no discrimination). Single-turnover experiments employing stoichiometrically iodinated ubiquitin derivatives indicated that E2(25K) discriminates extremely strongly (greater than 20-fold reduction in kcat/Km for diubiquitin synthesis) against ubiquitin that is monoiodinated at Tyr-59. The modest overall selection effect observed in continuous reactions is in part due to the occurrence of discrimination only when iodotyrosylubiquitin is the acceptor (Lys-48 donor) in diubiquitin synthesis; iodotyrosylubiquitin is kinetically competent when it is the species being transferred to native ubiquitin. The competence as acceptor of a site-directed mutant form of ubiquitin bearing a Tyr to Phe substitution at position 59 indicated that discrimination against iodotyrosylubiquitin by E2(25K) is not due to loss of the hydrogen-bonding interactions of Tyr-59. Rather, iodotyrosylubiquitin may be unable to react with the ubiquitin adduct of E2(25K) for steric reasons. Discrimination against iodotyrosylubiquitin as acceptor is unique to E2(25K) among three enzymes surveyed: iodotyrosylubiquitin is a fully competent acceptor in diubiquitin synthesis catalyzed by E2(25K) and is also utilized for multiubiquitin chain synthesis by E2(14K) and ubiquitin-protein ligase. These findings should assist in the design of future studies concerning E2(25K) structure and function.

Amino Acid Sequence↗
PubMed1992

Ubiquitin and ubiquitin conjugates in human lens.

Ubiquitin, an 8.5 kDa polypeptide found almost universally in plants and animals, is a normal component in the lens. The best documented function for ubiquitin involves its conjugation to proteins as a signal to initiate degradation. Conjugates for ubiquitin-dependent degradation tend to be of very high molecular mass and are rapidly degraded. Another role of ubiquitin conjugation may be as a stabilizer during stress for protection of constituent proteins, resulting in ubiquitin conjugates that are long-lived. Examination of clear and cataractous human lenses of < 1 to > 50 years revealed the dramatic accumulation of ubiquitin and ubiquitin conjugates with age, beginning at approximately 10 years. Epithelial tissue contained predominantly conjugates of > 250 kDa, although ubiquitin conjugates were found at 98 and 40-60 kDa in tissues from older donors. The water-soluble, urea-soluble and urea-insoluble fractions of lens cortex and core also contain ubiquitin conjugates that accrue with age. High molecular mass conjugates (> 250 kDa) are particularly prominent in older lens tissue. Cataractous lenses, as compared with normal lenses of the same age, show more of these high molecular mass conjugates in the urea-soluble and urea-insoluble fractions of cortex and core. Heterogeneous conjugates in the 20-85 kDa range accumulate in an age-related fashion in all lens cortex and core fractions. While levels of free ubiquitin are significant in the epithelium and the water-soluble cortex and core for all ages, there is no detectable free ubiquitin in the urea-soluble and urea-insoluble fraction under conditions used in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1991

Uncoupling ubiquitin-protein conjugation from ubiquitin-dependent proteolysis by use of beta, gamma-nonhydrolyzable ATP analogues.

Pathways of ubiquitin-dependent protein degradation have in common two requirements for ATP. Ubiquitin activation by the enzyme E1 is accompanied by ATP hydrolysis to yield AMP and PPi, and during conjugate breakdown, the ubiquitin-dependent protease hydrolyzes ATP to ADP and Pi. We show here that either of two beta, gamma-nonhydrolyzable ATP analogues, 5'-adenylyl imidodiphosphate or 5'-adenylyl methylenediphosphate, can support ubiquitin-protein conjugation. With the ubiquitin-dependent protease, however, neither analogue could substitute for ATP. Thus, the substitution of a beta, gamma-nonhydrolyzable analogue for ATP offers a simple method to uncouple ubiquitin conjugation from proteolysis in crude systems. On the basis of pyrophosphate exchange kinetics, E1 has apparent Km and Vmax values that are similar for ATP and the analogues, but substrate inhibition by 5'-adenylyl methylenediphosphate made use of the beta, gamma-imido analogue preferable. In one application, beta, gamma-imido-ATP was used in combination with ubiquitin aldehyde (an inhibitor of ubiquitin-protein isopeptidases) to establish that several unfolded RNase A derivatives are recognized equally as ubiquitination substrates. This result extends an earlier study [Dunten, R. L., & Cohen, R. E. (1989) J. Biol. Chem. 264, 16739-16747] to show that conjugate yields, upon which relative ubiquitination rates were based, were not influenced by differential ubiquitin-dependent proteolysis. In a second application, ATP and beta, gamma-imido-ATP were compared in a pulse-chase experiment to investigate the contributions of ATP-dependent proteolysis and isopeptidase activities to conjugate stability.

Adenosine Triphosphate↗
PubMed1991

RAD6 gene product of Saccharomyces cerevisiae requires a putative ubiquitin protein ligase (E3) for the ubiquitination of certain proteins.

The RAD6 (UBC2) gene of Saccharomyces cerevisiae which is involved in DNA repair, induced mutagenesis, and sporulation, encodes a ubiquitin-conjugating enzyme (E2). Since the RAD6 gene product can transfer ubiquitin directly to histones in vitro without the participation of a ubiquitin protein ligase (E3), it has been suggested that in vivo it also acts by the unassisted conjugation of ubiquitin to histones or to other target proteins. Here we show that the RAD6 protein can ligate ubiquitin in vitro to a hitherto unknown set of exogenous target proteins (alpha-, beta-, and kappa-casein and beta-lactoglobulin) when supplemented by a putative ubiquitin protein ligase (E3-R) from S. cerevisiae. RAD6 supplemented with E3-R ligates 1 or, sometimes, 2 ubiquitin molecules to the target protein molecule. UBC3 (CDC34) protein in the presence of E3-R has barely detectable activity on the non-histone substrates. Other ubiquitin-conjugating enzymes tested (products of the UBC1 and UBC4 genes) do not cooperate with E3-R in conjugating ubiquitin to the same substrates. Thus, E3-R apparently interacts selectively with RAD6 protein. These findings suggest that some of the in vivo activities of the RAD6 gene may involve E3-R.

Electrophoresis, Polyacrylamide Gel↗
PubMed1991

Alzheimer's disease brain-derived ubiquitin has amyloid-enhancing factor activity: behavior of ubiquitin during accelerated amyloidogenesis.

Amyloid-enhancing factor (AEF) is believed to be a crucial common pathogenetic link in diverse forms of human amyloidosis. Passive transfer of crude AEF is known to trigger accelerated splenic amyloid deposition in mice. We have recently identified AEF activity in ubiquitin isolated from murine amyloidotic tissues. Using similar techniques we have purified ubiquitin, from crude Alzheimer's disease (AD) brain extracts, to apparent homogeneity. Based on the partial amino acid sequence homology, immunochemical and pathophysiological criteria, the approximately 5.5-kDa AD-derived protein was identified as ubiquitin (AD-ubiquitin) with AEF activity. Ten to twenty micrograms of this protein per mouse, with or without CaCl2, in conjunction with four subcutaneous injections of 0.5 ml of 1% aqueous AgNO3, induced accelerated splenic amyloid deposition. By immunohistochemistry, using anti-mouse AA amyloid antibody, the AD-ubiquitin-induced amyloid was identified as AA type. With anti-bovine ubiquitin antibody, using similar spleen sections as above, ubiquitin was found to co-deposit with AA amyloid in the splenic perifollicular areas. These results strongly suggest that ubiquitin may be involved in the pathogenesis of amyloidosis.

Aged↗
PubMed1991

Changes in ubiquitin and ubiquitin-protein conjugates in the CA1 neurons after transient sublethal ischemia.

Ubiquitin is involved in the degradation of denatured proteins in the recovery process after various stresses. To clarify the different responses of the ubiquitin system in the hippocampal neurons after ischemia, we chose 7.5 min of sublethal forebrain ischemia in the rat. After 7.5 min of ischemia, ubiquitin-like immunoreactivity (UIR) in most of the hippocampal pyramidal cells, except for the interneurons, diminished after 3 h of reperfusion, but enhanced UIR and subsequent recovery of UIR were observed in the different hippocampal regions after 24 h of reperfusion. The most prolonged recovery of UIR in the hippocampal cells was observed in the CA1 neurons after 72 h of reperfusion. Immunoblot analysis of the proteins extracted from CA1 region showed that high-mol-wt ubiquitin conjugates (HMWUC) above 40 kDa increased, whereas free ubiquitin and ubiquitinated histone 2A decreased slightly after 4 h and 24 h of reperfusion. At 72 h of reperfusion, HMWUC decreased to the original level and free ubiquitin slightly increased beyond the control level. These results suggested that (1) diminished UIR does not always mean depletion of entire ubiquitin-protein conjugates; (2) even after sublethal ischemia, damaged proteins in the CA1 neurons may increase, and it may take a long time for elimination of these proteins.

Animals↗
PubMed1992

A rabbit reticulocyte ubiquitin carrier protein that supports ubiquitin-dependent proteolysis (E214k) is homologous to the yeast DNA repair gene RAD6.

The two isoforms of the 14-kDa ubiquitin carrier protein (E2(14k)) are unique among rabbit E2s in efficiently supporting ubiquitin-protein ligase (E3)-mediated ubiquitination of proteins destined for degradation. To begin determining the structural basis for this property, we have isolated a cDNA encoding the predominant reticulocyte isoform of the E2 from a rabbit skeletal muscle library. The sequence predicts a protein of 152 amino acids with a molecular weight of 17,293. Expression of the cDNA in Escherichia coli and purification of the recombinant protein revealed an E2 with high affinity for E3 and ubiquitin activating enzyme (E1). The latter high affinity interaction appears to be between the ubiquitin charged form of E1 and the uncharged form of E2 and does not result in a stable complex between these two enzymes. The predicted sequence shows regions of strong homology with other sequenced E2s, suggesting that these regions may be involved in binding to E1 and/or in ubiquitin transfer from E1, functions common to all E2s. Surprisingly, the E2(14k)) sequence is markedly more similar to Saccharomyces cerevisiae RAD6 (69% identity) than to its proposed homologs UBC4/UBC5 (38% identity). The sequence is identical to that recently reported for a human 17-kDa E2 which can complement rad6 mutants thereby identifying rabbit E2(14k) as a RAD6 homologue. The biochemical properties of this previously uncharacterized human 17-kDa E2 are now defined and its misassignment as a homologue of rabbit E2(17k) is corrected. Our findings resolve current confusion regarding relationships among E2s and define yeast RAD6, rabbit E2(14k), and the human 17-kDa E2 as a subclass of E2s which biochemically support E3-mediated conjugation and ubiquitin-dependent proteolysis and physiologically play a role in DNA repair.

Amino Acid Sequence↗
PubMedDate not supplied

Inhibition of ubiquitin-ATP-dependent proteolysis and ubiquitination by cisplatin.

We tested the inhibitory activity of various antitumor agents on the ubiquitin-ATP-dependent proteolytic activity in rabbit reticulocyte lysates. We found that cisplatin, 4'-(9-acridinyl-amino) methanesulfon-m-anisidide (m-AMSA) and mitomycin C inhibited the ubiquitin-ATP-dependent proteolysis. IC50 values (50% inhibition concentrations) of these antitumor agents were 90, 210 and above 290 microM, respectively. Furthermore, cisplatin was found to inhibit the conjugation of ubiquitin to endogenous proteins in fraction II at 100 and 330 microM. These results suggest that cisplatin interacts with the enzyme(s) involved in ubiquitin conjugation and thus inhibits the ubiquitin-ATP-dependent protein degradation. We assume that the agents that can affect the ubiquitin system might be useful for the treatment of tumors and that the ubiquitin system could be a new target for cancer chemotherapy.

Amsacrine↗
PubMed1992

Purification of Chlamydomonas 28-kDa ubiquitinated protein and its identification as ubiquitinated histone H2B.

One of the most predominantly ubiquitinated protein species in Chlamydomonas, of which the apparent molecular mass in SDS-PAGE was 28 kDa, was found to exist abundantly in nuclei. The 28-kDa ubiquitinated protein was purified to homogeneity from the isolated nuclei of Chlamydomonas, and its partial amino acid sequence was determined. The N-terminal peptide sequence was identical with that of ubiquitin. Sequences homologous to those Chlamydomonas ubiquitin [corrected] and wheat histone H2B, and paired sequences of both of them were found in arginylendopeptidase-digested or protease V8-digested polypeptide fragments of the 28-kDa ubiquitinated protein. Based on these results, it was concluded that Chlamydomonas 28-kDa ubiquitinated protein is monoubiquitinated histone H2B.

Amino Acid Sequence↗
PubMed1992

Ubiquitin of Entamoeba histolytica deviates in six amino acid residues from the consensus of all other known ubiquitins.

The amino acid sequence of ubiquitin from Entamoeba histolytica, as deduced from a cDNA nucleotide sequence, deviated at six positions from the consensus of all other known ubiquitins (ranging from Trypanosoma cruzi to Homo sapiens). The corresponding residues were scattered over the primary sequence, but came close together on the surface of the folded protein structure. We conclude that (i) E. histolytica branched off very early from the main eukaryotic line, and (ii) this organism may yield clues as to the evolutionary development of the ubiquitin system.

Amino Acid Sequence↗
PubMed1991

Ubiquitin in a lower plant. Characterization of ubiquitin-encoding DNA and RNA from Chlamydomonas reinhardii.

A detailed characterization of Chlamydomonas reinhardii cDNAs encoding ubiquitin 52-amino-acid fusion proteins is presented in this study. While two cDNAs (designated UBI1 and UBI3) encode the complete ubiquitin extension protein, the third one (UBI2) lacks a minor part of the 5' region as well as a poly(A) tail. Differences between UBI1 and UBI3 are observed in the length of the poly(A) domain (13 versus 46 adenines) and in the lack of three nucleotides at the 3' noncoding region of UBI3. According to Northern blot experiments using UBI1 as a homologous probe, at least six members of the C. reinhardii ubiquitin gene family are transcriptionally active at regular conditions. During application of severe stress (heat shock in light and darkness, and photoinhibition), the transcription of the UBI1 mRNA substantially decreases. This effect is most drastically induced by application of heat shock to illuminated cells.

Amino Acid Sequence↗
PubMed1991

Ubiquitin-encoding mRNA and mRNA recognized by genes encoding ubiquitin-conjugating enzymes are differentially expressed in division-synchronized cultures of Chlamydomonas reinhardtii.

Cells of Chlamydomonas reinhardtii were synchronized by a light/dark illumination cycle of 14:10 h. All cells divided within the first 2 h of the dark period, the synchronization index was calculated as 0.916. RNA was isolated every 2 h and hybridized to 32P-labeled probes encoding (i) ubiquitin from Chlamydomonas reinhardtii (UBM) and (ii) two different ubiquitin-conjugating enzymes from Saccharomyces cerevisiae (UBC2 and UBC3). Sequences with homology to yeast UBC2 and UBC3, which are required for sporulation/DNA repair and G1/S transition in yeast, respectively, were detected in C. reinhardtii. In the algae, the relative abundance of transcripts encoding ubiquitin fusion proteins and UBC2 homologues is most prominent at the end of the light phase and throughout the dark. The highest amount of a putative polyubiquitin encoding transcript was detected during the dark phase of the synchronized culture. A high amount of this transcript is also present during the 8th hour of the light phase which may imply that the transcription of polyubiquitin gene is not only restricted to stress conditions in C. reinhardtii. The relative abundance of transcripts with homology to UBC3 is most pronounced within the light period corresponding to G1 and S phases of the C. reinhardtii cell cycle.

Animals↗
PubMed1992

Expression of a ubiquitin derivative that conjugates to protein irreversibly produces phenotypes consistent with a ubiquitin deficiency.

Ubiquitin (Ub) exists in a dynamic equilibrium between the free form and the conjugated form. This equilibrium is maintained and regulated through the antagonistic actions of the conjugation system and a class of enzymes referred to collectively as the Ub-protein hydrolases. Using a previously described epitope-tagged Ub approach (Ellison, M., and Hochstrasser, M. (1991) J. Biol. Chem. 266, 21150-21157) we show here that a single amino acid substitution at the carboxyl terminus of Ub (Gly-76 to Ala-76) results in a derivative of Ub (UbA-76) that becomes irreversibly conjugated to protein when expressed in the yeast Saccharomyces cerevisiae, producing a profound effect on the Ub-conjugate equilibrium. The major target of UbA-76 conjugation is itself (and presumably wild-type Ub) producing unanchored chains at the expense of the free form. Unsurprisingly, the expression of UbA-76 results in yeast phenotypes that would be expected in situations of Ub deprivation. Such cells show slow growth characteristics and sensitivity to various forms of environmental stress and to ultraviolet light. In view of these findings, the expression of UbA-76 in higher organisms may represent a convenient epigenetic strategy for examining the physiological consequences of Ub deprivation or Ub-protein hydrolase disfunction in living cells without the need for gene disruption or replacement. The observation that UbA-76 couples to itself irreversibly also provides an effective tool for elucidating the role of Ub as the proteolytic signal.

Amino Acids↗
PubMed1991

Ubiquitin in health and disease.

Studies in recent years have shown that ubiquitin has increasingly important functions in eukaryotic cells; roles which were previously not suspected in healthy and diseased cells. The interplay between molecular pathological and molecular cell biological findings has indicated that ubiquitin may be pivotal in the cell stress response in chronic degenerative and viral diseases. Furthermore, the studies have led to the notion that ubiquitination may not only serve as a signal for nonlysosomal protein degradation but may be a unifying covalent protein modification for the major intracellular protein catabolic systems; these can act to identify proteins for cytosolic proteinases or direct intact and fragmented proteins into the lysosome system for breakdown to amino acids. This unifying role could explain why ubiquitin is restricted to eukaryotic cells, which possess extensive endomembrane systems in addition to a nuclear envelope. Protein ubiquitination is a feature of most filamentous inclusions and certain other intracellular conglomerates that are found in some degenerative and viral diseases. The detection of ubiquitin-protein conjugates is not of great diagnostic importance in these diseases. Protein ubiquitination is not only essential for the normal physiological turnover of proteins but appears to have been adapted as part of an intracellular surveillance system that can be activated by altered, damaged, or foreign proteins and organelles. The purpose of this system is to isolate and eliminate these noxious structures from the cell: as a cytoprotective mechanism this appears to have evolved in the cell akin perhaps to an 'intracellular immune system'. Other heat shock proteins such as hsp 70 may be involved in this process. It is apparent that ubiquitin has a role in embryonic development. Protein ubiquitination is presumably involved in the reorganisation of cytoplasm that accompanies cell differentiation. Ubiquitin is also necessary for the gross intracellular degradative processes which are consequent upon programmed cell death. Cell elimination is of key importance for a number of developmental morphogenetic changes. An understanding of the molecular details of these processes will no doubt provide further insights into the wide ranging roles of ubiquitin in the life process. As it says in the book 'Ubiquitin'; there is no doubt that ubiquitin is a 'lucky' protein. It is lucky in many ways: lucky for scientific progress, lucky for biomedical scientists and lucky for life! If you have not already done so, why don't you get lucky and look for a role for ubiquitin in your experimental system. As Avram Hershko has said "there is plenty to go round"!

Animals↗