SGT1-HSP90 complex is required for CENP-A deposition at centromeres

Niikura, Yohei; Kitagawa, Risa; Ogi, Hiroo; Kitagawa, Katsumi

doi:10.1080/15384101.2017.1325039

Cited by 14 publications

(19 citation statements)

References 60 publications

(78 reference statements)

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“…Molecular chaperones and their accessory proteins are capable of activating and folding proteins, playing important roles in the ubiquitin–proteasome pathway, and are able to maintain protein stability. Indeed, it has been shown that the chaperone protein HSP90 can regulate the E3 ligase activity of the CUL4A complex, which in turn contributes to CENP-A ubiquitylation and CENP-A deposition at the centromeres [43]. Our present data exhibited that another chaperone protein, HSC70, was able to interact with CENP-N and that knockdown of HSC70 significantly decreased the expression of CENP-N.…”

Section: Discussionsupporting

confidence: 61%

Heat Shock Cognate 70 Functions as A Chaperone for the Stability of Kinetochore Protein CENP-N in Holocentric Insect Silkworms

Lü

et al. 2019

IJMS

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The centromere, in which kinetochore proteins are assembled, plays an important role in the accurate congression and segregation of chromosomes during cell mitosis. Although the function of the centromere and kinetochore is conserved from monocentric to holocentric, the DNA sequences of the centromere and components of the kinetochore are varied among different species. Given the lack of core centromere protein A (CENP-A) and CENP-C in the lepidopteran silkworm Bombyx mori, which possesses holocentric chromosomes, here we investigated the role of CENP-N, another important member of the centromere protein family essential for kinetochore assembly. For the first time, cellular localization and RNA interference against CENP-N have confirmed its kinetochore function in silkworms. To gain further insights into the regulation of CENP-N in the centromere, we analyzed the affinity-purified complex of CENP-N by mass spectrometry and identified 142 interacting proteins. Among these factors, we found that the chaperone protein heat shock cognate 70 (HSC70) is able to regulate the stability of CENP-N by prohibiting ubiquitin–proteasome pathway, indicating that HSC70 could control cell cycle-regulated degradation of CENP-N at centromeres. Altogether, the present work will provide a novel clue to understand the regulatory mechanism for the kinetochore activity of CENP-N during the cell cycle.

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Section: Discussionsupporting

confidence: 61%

Heat Shock Cognate 70 Functions as A Chaperone for the Stability of Kinetochore Protein CENP-N in Holocentric Insect Silkworms

Lü

et al. 2019

IJMS

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“…Inflammation occurring in the testes of obese men may be reflected in, and to some extent explained by, the proteomic alterations we observed. We found reduced levels of SUGT1 (alias SGT1), a cochaperone of HSP90 with roles in Akt signaling [34], centromere function [35], and regulation of NLRP3 inflammasomes [36]. Obesity is associated with increased expression of NLRP3 [37], and as the SUGT1-HSP90 complex is responsible for maintaining these inflammasomes in a repressed state, limited levels of SUGT1 could potentially lead to an aberrant immune response and auto-activation of inflammatory pathways [36].…”

Section: Discussionmentioning

confidence: 94%

Obesity significantly alters the human sperm proteome, with potential implications for fertility

Pini

Parks

Russ

et al. 2020

J Assist Reprod Genet

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Purpose In men, obesity may lead to poor semen parameters and reduced fertility. However, the causative links between obesity and male infertility are not totally clear, particularly on a molecular level. As such, we investigated how obesity modifies the human sperm proteome, to elucidate any important implications for fertility. Methods Sperm protein lysates from 5 men per treatment, classified as a healthy weight (body mass index (BMI) ≤ 25 kg/m 2) or obese (BMI ≥ 30 kg/m 2), were FASP digested, submitted to liquid chromatography tandem mass spectrometry, and compared by label-free quantification. Findings were confirmed for several proteins by qualitative immunofluorescence and a quantitative protein immunoassay. Results A total of 2034 proteins were confidently identified, with 24 proteins being significantly (p < 0.05) less abundant (fold change < 0.05) in the spermatozoa of obese men and 3 being more abundant (fold change > 1.5) compared with healthy weight controls. Proteins with altered abundance were involved in a variety of biological processes, including oxidative stress (GSS, NDUFS2, JAGN1, USP14, ADH5), inflammation (SUGT1, LTA4H), translation (EIF3F, EIF4A2, CSNK1G1), DNA damage repair (UBEA4), and sperm function (NAPA, RNPEP, BANF2). Conclusion These results suggest that oxidative stress and inflammation are closely tied to reproductive dysfunction in obese men. These processes likely impact protein translation and folding during spermatogenesis, leading to poor sperm function and subfertility. The observation of these changes in obese men with no overt andrological diagnosis further suggests that traditional clinical semen assessments fail to detect important biochemical changes in spermatozoa which may compromise fertility.

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“…CENP-A In Vivo Ubiquitylation Assays in vivo CENP-A ubiquitylation assays were performed as described previously (Niikura et al, 2015(Niikura et al, , and 2017). To study ubiquitylation of exogenous EYFP-CENP-A, CENP-A -/F REP-1 cells were cotransfected with the indicated expression vector(s) (Key Resources (Lamb et al, 1995) and subjected to western blot analysis with the indicated antibodies (Key Resources Table ).…”

Section: Declaration Of Interestsmentioning

confidence: 99%

“…However, there are substantive issues with the experiments that yielded these results. We published our response describing the potential problems with their results and conclusions (Niikura et al, 2017). A major caveat is that they used a fusion protein much larger than CENP-A: in the RPE-1 CENP-A À/F knockout system, the enhanced yellow fluorescent protein (EYFP) is approximately 30 kDa, and endogenous CENP-A is about 16 kDa.…”

Section: Introductionmentioning

confidence: 99%