Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Jun;52(6):931-939.
doi: 10.1038/s12276-020-0457-2. Epub 2020 Jun 26.

SUMO and cellular adaptive mechanisms

Hong-Yeoul Ryu  1   2 , Seong Hoon Ahn  3 , Mark Hochstrasser  4
Affiliations
Review

SUMO and cellular adaptive mechanisms

Hong-Yeoul Ryu et al. Exp Mol Med. 2020 Jun.

Abstract

The ubiquitin family member SUMO is a covalent regulator of proteins that functions in response to various stresses, and defects in SUMO-protein conjugation or deconjugation have been implicated in multiple diseases. The loss of the Ulp2 SUMO protease, which reverses SUMO-protein modifications, in the model eukaryote Saccharomyces cerevisiae is severely detrimental to cell fitness and has emerged as a useful model for studying how cells adapt to SUMO system dysfunction. Both short-term and long-term adaptive mechanisms are triggered depending on the length of time cells spend without this SUMO chain-cleaving enzyme. Such short-term adaptations include a highly specific multichromosome aneuploidy and large changes in ribosomal gene transcription. While aneuploid ulp2Δ cells survive, they suffer severe defects in growth and stress resistance. Over many generations, euploidy is restored, transcriptional programs are adjusted, and specific genetic changes that compensate for the loss of the SUMO protease are observed. These long-term adapted cells grow at normal rates with no detectable defects in stress resistance. In this review, we examine the connections between SUMO and cellular adaptive mechanisms more broadly.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1. Stress-induced cellular adaptive strategies.
First-line adaptive mechanisms maximize cell survival under acute stress conditions. When these protective responses are not sufficient to protect cells from stress, the cells activate second-line adaptive mechanisms, which primarily consist of genetic changes that confer resistance to stress. However, because some second-line responses are deleterious to cell fitness, they may evolve or reactivate other adaptive mechanisms through genetic or epigenetic changes.
Fig. 2
Fig. 2. Evolution of adaptive mechanisms upon the loss of Ulp2.
The loss of Ulp2 in yeast leads to the accumulation of polySUMO-conjugated proteins, increased expression of ribosomal proteins and reduced cell fitness (depicted by the irregular cell outline). Disomies of ChrI and ChrXII provide a transient adaptive solution by virtue of an increased dosage of three protein-coding genes, CCR4, CLN3, and CCW12, and a snoRNA gene cluster consisting of SNR61, SNR55, and SNR57. Following evolution over many cell generations, disomies of both ChrI and XII are replaced with two other adaptive mechanisms: mutations of SUMO-ligating enzymes and specific transcriptome changes. Point mutations in UBC9 or UBA2, on ChrIV, or AOS1, on ChrXVI, reduce SUMO conjugation and suppress the growth defects of ulp2Δ cells. In parallel, the upregulation of numerous snoRNA genes, which can repress the transcription of RP genes, and refined transcriptome alterations concomitant with epigenetic changes (unpublished data) appear to facilitate further adaptation.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Johnson ES. Protein modification by SUMO. Annu. Rev. Biochem. 2004;73:355–382. - PubMed
    1. Huang WC, Ko TP, Li SS, Wang AH. Crystal structures of the human SUMO-2 protein at 1.6 A and 1.2 A resolution: implication on the functional differences of SUMO proteins. Eur. J. Biochem. 2004;271:4114–4122. - PubMed
    1. Hendriks IA, Vertegaal AC. A comprehensive compilation of SUMO proteomics. Nat. Rev. Mol. Cell Biol. 2016;17:581–595. - PubMed
    1. Hickey CM, Wilson NR, Hochstrasser M. Function and regulation of SUMO proteases. Nat. Rev. Mol. Cell Biol. 2012;13:755–766. - PMC - PubMed
    1. Flotho A, Melchior F. Sumoylation: a regulatory protein modification in health and disease. Annu Rev. Biochem. 2013;82:357–385. - PubMed

Publication types

LinkOut - more resources