Proteolysis of γ‐tubulin small complex proteins is mediated by the ubiquitin‐proteasome system

Yin, Chuancun; Lui, Edna S.W.; Jiang, Taolue; Qi, Robert Z.

doi:10.1002/1873-3468.14146

Cited by 4 publications

(4 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In these blots, it is evident that an additional higher-molecular weight band of γ-tubulin that runs at 62.5kDa co-precipitates with Stu2. As γ-tubulin has been reported previously to be ubiquitinated in mammalian cell lines HEC293T cells [40][41][42][43], we speculate that this may be the molecular basis of the shift seen here. Notably, it appears that the modified form of γ-tubulin is enhanced in the interactions with Stu2 (Fig 10A and 10B, compare γ-tubulin in the pulldowns to the WCEs).…”

Section: Plos Geneticssupporting

confidence: 73%

The TOG protein Stu2 is regulated by acetylation

Greenlee

Witt²,

Sabo³

et al. 2022

PLoS Genet

View full text Add to dashboard Cite

Stu2 in S. cerevisiae is a member of the XMAP215/Dis1/CKAP5/ch-TOG family of MAPs and has multiple functions in controlling microtubules, including microtubule polymerization, microtubule depolymerization, linking chromosomes to the kinetochore, and assembly of γ-TuSCs at the SPB. Whereas phosphorylation has been shown to be critical for Stu2 localization at the kinetochore, other regulatory mechanisms that control Stu2 function are still poorly understood. Here, we show that a novel form of Stu2 regulation occurs through the acetylation of three lysine residues at K252, K469, and K870, which are located in three distinct domains of Stu2. Alteration of acetylation through acetyl-mimetic and acetyl-blocking mutations did not impact the essential function of Stu2. Instead, these mutations lead to a decrease in chromosome stability, as well as changes in resistance to the microtubule depolymerization drug, benomyl. In agreement with our in silico modeling, several acetylation-mimetic mutants displayed increased interactions with γ-tubulin. Taken together, these data suggest that Stu2 acetylation can govern multiple Stu2 functions, including chromosome stability and interactions at the SPB.

show abstract

Section: Plos Geneticssupporting

confidence: 73%

The TOG protein Stu2 is regulated by acetylation

Greenlee

Witt²,

Sabo³

et al. 2022

PLoS Genet

View full text Add to dashboard Cite

show abstract

“…In these blots, it is evident that an additional higher-molecular weight band of γ-tubulin that runs at 62.5kDa co-precipitates with Stu2. As γ-tubulin has been reported previously to be ubiquitinated in mammalian cell lines HEC293T cells (Yin et al, 2021) (Starita et al, 2004) (Sankaran et al, 2005) (Sankaran et al, 2007), we speculate that this may be the molecular basis of the shift seen here. Notably, it appears that the modified form of γ-tubulin is enhanced in the interactions with Stu2 (Figure 9A,B, compare γ-tubulin in the pulldowns to the WCEs).…”

Section: Stu2 Acetylation Regulates Interactions With γ-Tubulinsupporting

confidence: 73%

The TOG protein Stu2 is regulated by acetylation

Miller

Greenlee

Witt

et al. 2022

Preprint

View full text Add to dashboard Cite

Stu2 in S. cerevisiae is a member of the XMAP215/Dis1/Alp14/Msps/CKAP5/ch-TOG family of MAPs and has multiple functions in controlling microtubules, including microtubule polymerization, microtubule depolymerization, linking chromosomes to the kinetochore, and assembly of γ-TuSCs at the SPB. Whereas phosphorylation has been shown to be critical for Stu2 localization at the kinetochore, other regulatory mechanisms that control Stu2 function are still poorly understood. Here, we show that a novel form of Stu2 regulation occurs through the acetylation of three lysine residues at K252, K469, and K870, which are located in three distinct domains of Stu2. Alteration of acetylation through acetyl-mimetic and acetyl-blocking mutations did not impact the essential function of Stu2. Instead, these mutations lead to both positive and negative changes in chromosome stability, as well as changes in resistance to the microtubule depolymerization drug, benomyl. In agreement with our in silico modeling, several acetylation-mimetic mutants displayed increased interactions with γ-tubulin. Taken together, these data suggest that Stu2 acetylation can govern multiple Stu2 functions in both a positive and negative manner, including chromosome stability and interactions at the SPB.

show abstract

“…Mammalian γ-tubulins are phosphorylated at multiple sites [ 47 ], and protein kinases and phosphatases were repeatedly identified in γ-tubulin immunocomplexes, suggesting that phosphorylation might be involved in the regulation of γ-tubulin interactions [ 12 ]. Monoubiquitination of γ-tubulin inhibits microtubule nucleation [ 48 ], and γ-tubulin ubiquitination plays an important role in the degradation of γ-tubulin complexes [ 49 ].…”

Section: γ-Tubulin and Microtubule Nucleation By γ-Tubulin Complexesmentioning

confidence: 99%

Dysregulation of Microtubule Nucleating Proteins in Cancer Cells

Dráberová

2021

Cancers

View full text Add to dashboard Cite

In cells, microtubules typically nucleate from microtubule organizing centers, such as centrosomes. γ-Tubulin, which forms multiprotein complexes, is essential for nucleation. The γ-tubulin ring complex (γ-TuRC) is an efficient microtubule nucleator that requires additional centrosomal proteins for its activation and targeting. Evidence suggests that there is a dysfunction of centrosomal microtubule nucleation in cancer cells. Despite decades of molecular analysis of γ-TuRC and its interacting factors, the mechanisms of microtubule nucleation in normal and cancer cells remains obscure. Here, we review recent work on the high-resolution structure of γ-TuRC, which brings new insight into the mechanism of microtubule nucleation. We discuss the effects of γ-TuRC protein dysregulation on cancer cell behavior and new compounds targeting γ-tubulin. Drugs inhibiting γ-TuRC functions could represent an alternative to microtubule targeting agents in cancer chemotherapy.

show abstract

Proteolysis of γ‐tubulin small complex proteins is mediated by the ubiquitin‐proteasome system

Cited by 4 publications

References 46 publications

The TOG protein Stu2 is regulated by acetylation

The TOG protein Stu2 is regulated by acetylation

The TOG protein Stu2 is regulated by acetylation

Dysregulation of Microtubule Nucleating Proteins in Cancer Cells

Contact Info

Product

Resources

About