Details

Autor(en) / Beteiligte

• Matveenko, Andrew G.
• Drozdova, Polina B.
• Belousov, Mikhail V.
• Moskalenko, Svetlana E.
• Bondarev, Stanislav A.
• Barbitoff, Yury A.
• Nizhnikov, Anton A.
• Zhouravleva, Galina A.

Titel

SFP1‐mediated prion‐dependent lethality is caused by increased Sup35 aggregation and alleviated by Sis1

Ist Teil von

• Genes to cells : devoted to molecular & cellular mechanisms, 2016-12, Vol.21 (12), p.1290-1308

Ort / Verlag

England: Wiley Subscription Services, Inc

Erscheinungsjahr

2016

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• [PSI+] is the prion form of the translation termination factor Sup35 (eRF3); [PSI+] strains display nonsense suppression. Another prion‐like element, [ISP+], is linked to antisuppression in a specific background. Transcriptional regulator Sfp1 was shown to be responsible for [ISP+] propagation. In this work, we identified SFP1 as a multicopy inducer of [PSI+]‐dependent lethality. Sfp1 is likely to up‐regulate transcription of genes encoding release factors; however, its overproduction increases Sup35, but not Sup45 protein level. Using the synthetic lethality test, we compared the effects of SFP1 and SUP35 over‐expression on the viability of [PSI+] strains. Together with an observation that Sfp1 overproduction leads to an increased accumulation of Sup35 in [PSI+] aggregates, we suggest that excess Sfp1 causes [PSI+] toxicity. Even though SUP45 over‐expression is known to compensate for the [PSI+]‐dependent lethality, it fails to do so when the lethality is caused by SFP1 over‐expression. We discovered that the increased levels of Hsp40 chaperone Sis1 alleviate prion toxicity caused by either SFP1 or SUP35 over‐expression and revert back to normal distribution of Sup35 between monomers and aggregate fractions. Finally, we showed that Sfp1 partially colocalizes with Sup35 aggregates, which may contribute to another mechanism of Sfp1‐derived [PSI+] prion toxicity. Sfp1 is a transcriptional regulator that, when overproduced, causes [PSI+] prion‐dependent lethality via up‐regulating yeast release factor Sup35 (eRF3). Increased levels of Hsp40 chaperone Sis1 alleviate the prion toxicity caused by either SFP1 or SUP35 over‐expression and revert the distribution of Sup35 between monomers and aggregate fractions back to normal. Finally, Sfp1 forms detergent‐resistant aggregates and may partially colocalize with Sup35 aggregates, suggesting an additional mechanism of Sfp1‐derived [PSI+] prion toxicity.