Редактирование: HSP90AA1

Heat shock protein HSP 90-alpha (EC 3.6.4.10) (Heat shock 86 kDa) (HSP 86) (HSP86) (Lipopolysaccharide-associated protein 2) (LAP-2) (LPS-associated protein 2) (Renal carcinoma antigen NY-REN-38) [HSP90A] [HSPC1] [HSPCA]

==Publications==

{{medline-entry
|title=[[SIRT6]] histone deacetylase functions as a potential oncogene in human melanoma.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29234488
|abstract=Melanoma is an aggressive skin cancer that can rapidly metastasize to become fatal, if not diagnosed early. Despite recent therapeutic advances, management of melanoma remains difficult. Therefore, novel molecular targets and strategies are required to manage this neoplasm. This study was undertaken to determine the role of the sirtuin [[SIRT6]] in melanoma. Employing a panel of human melanoma cells and normal human melanocytes, we found significant [[SIRT6]] mRNA and protein upregulation in melanoma cells. Further, using a tissue microarray coupled with quantitative Vectra analysis, we demonstrated significant [[SIRT6]] overexpression in human melanoma tissues. Lentiviral short hairpin RNA-mediated knockdown of [[SIRT6]] in A375 and Hs 294T human melanoma cells significantly decreased cell growth, viability, and colony formation, induced G1-phase arrest and increased senescence-associated beta-galactosidase staining. As autophagy is important in melanoma and is associated with [[SIRT6]], we used a qPCR array to study [[SIRT6]] knockdown in A375 cells. We found significant modulation in several genes and/or proteins (decreases in [[AKT1]], [[ATG12]], [[ATG3]], [[ATG7]], [[BAK1]], [[BCL2L1]], [[CLN3]], [[CTSB]], [[CTSS]], [[DRAM2]], [[HSP90AA1]], [[IRGM]], [[NPC1]], [[SQSTM1]], [[TNF]], and BECN1; increases in [[GAA]], ATG10). Our data suggests that increased [[SIRT6]] expression may contribute to melanoma development and/or progression, potentially via senescence-and autophagy-related pathways.

|keywords=* SIRT6
* autophagy
* melanoma
* senescence
* sirtuins
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5724804
}}
{{medline-entry
|title=Integration-independent Transgenic Huntington Disease Fragment Mouse Models Reveal Distinct Phenotypes and Life Span in Vivo.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26025364
|abstract=The cascade of events that lead to cognitive decline, motor deficits, and psychiatric symptoms in patients with Huntington disease (HD) is triggered by a polyglutamine expansion in the N-terminal region of the huntingtin ([[HTT]]) protein. A significant mechanism in HD is the generation of mutant [[HTT]] fragments, which are generally more toxic than the full-length [[HTT]]. The protein fragments observed in human HD tissue and mouse models of HD are formed by proteolysis or aberrant splicing of [[HTT]]. To systematically investigate the relative contribution of the various [[HTT]] protein proteolysis events observed in vivo, we generated transgenic mouse models of HD representing five distinct proteolysis fragments ending at amino acids 171, 463, 536, 552, and 586 with a polyglutamine length of 148. All lines contain a single integration at the ROSA26 locus, with expression of the fragments driven by the chicken β-actin promoter at nearly identical levels. The transgenic mice N171-Q148 and N552-Q148 display significantly accelerated phenotypes and a shortened life span when compared with N463-Q148, N536-Q148, and N586-Q148 transgenic mice. We hypothesized that the accelerated phenotype was due to altered [[HTT]] protein interactions/complexes that accumulate with age. We found evidence for altered [[HTT]] complexes in caspase-2 fragment transgenic mice (N552-Q148) and a stronger interaction with the endogenous [[HTT]] protein. These findings correlate with an altered [[HTT]] molecular complex and distinct proteins in the [[HTT]] interactome set identified by mass spectrometry. In particular, we identified [[HSP90AA1]] (HSP86) as a potential modulator of the distinct neurotoxicity of the caspase-2 fragment mice (N552-Q148) when compared with the caspase-6 transgenic mice (N586-Q148). 
|mesh-terms=* Animals
* Brain
* Codon, Nonsense
* Disease Models, Animal
* Female
* HEK293 Cells
* HSP90 Heat-Shock Proteins
* Humans
* Huntingtin Protein
* Huntington Disease
* Longevity
* Male
* Mice, Inbred C57BL
* Mice, Transgenic
* Motor Activity
* Nerve Tissue Proteins
* Phenotype
* Protein Interaction Mapping
* Proteolysis
|keywords=* caspase
* neurodegenerative disease
* polyglutamine disease
* proteolysis
* transgenic mice
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521048
}}