Yeast Smy2 and its human homologs GIGYF1 and -2 regulate Cdc48/VCP function during transcription stress
| Autor: | Michelle Harreman Lehner, Jane Walker, Kotryna Temcinaite, Anna Herlihy, Michael Taschner, Adam C. Berger, Anita H. Corbett, A. Barbara Dirac Svejstrup, Jesper Q. Svejstrup |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Model organisms
p97 Adenosine Triphosphatases Molecular biology [CP] Saccharomyces cerevisiae Proteins DEF1 last resort pathway SMY2 Genome Integrity & Repair Gene Expression Cell Cycle Proteins Saccharomyces cerevisiae Biochemistry & Proteomics GIGYF2 cdc48 GIGYF1 General Biochemistry Genetics and Molecular Biology proteasome Valosin Containing Protein Humans RNA polymerase II RNA Polymerase II Carrier Proteins Genetics & Genomics VCP |
| Zdroj: | Lehner, M H, Walker, J, Temcinaite, K, Herlihy, A, Taschner, M, Berger, A C, Corbett, A H, Dirac Svejstrup, A B & Svejstrup, J Q 2022, ' Yeast Smy2 and its human homologs GIGYF1 and-2 regulate Cdc48/VCP function during transcription stress ', Cell Reports, vol. 41, no. 4, 111536 . https://doi.org/10.1016/j.celrep.2022.111536 |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2022.111536 |
| Popis: | The “last resort” pathway results in ubiquitylation and degradation of RNA polymerase II in response to transcription stress and is governed by factors such as Def1 in yeast. Here, we show that the SMY2 gene acts as a multi-copy suppressor of DEF1 deletion and functions at multiple steps of the last resort pathway. We also provide genetic and biochemical evidence from disparate cellular processes that Smy2 works more broadly as a hitherto overlooked regulator of Cdc48 function. Similarly, the Smy2 homologs GIGYF1 and -2 affect the transcription stress response in human cells and regulate the function of the Cdc48 homolog VCP/p97, presently being explored as a target for cancer therapy. Indeed, we show that the apoptosis-inducing effect of VCP inhibitors NMS-873 and CB-5083 is GIGYF1/2 dependent. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|