Disease relevance of MYST1

• In conclusion, this investigation has demonstrated a benefit from adjuvant chemotherapy (MOF) for the management of rectal cancer [1].
• MORF is a member of the MYST family of histone acetyltransferase and previously has been found rearranged in some types of acute myeloid leukemia (AML) [2].
• Four patients died (actual patient survival FR group: 87.5% versus FL group: 89.5%), 3 due to septic MOF and 1 due to graft versus host disease [3].
• In the study population, levels of sE-selectin, sICAM-1, and vWf:Ag were higher for nonsurvivors as well as for patients with septic shock or with bacteremia, and they were correlated with SAPS and MOF [4].
• We tested whether the five proteins were predictors of clinical severity, which was evaluated by simplified acute physiological score (SAPS), number of organ failures (MOF), acute lung injury (ALI), and subsequent final outcome [4].

High impact information on MYST1

• CLOCK shares homology with acetyl-coenzyme A binding motifs within the MYST family of HATs [5].
• A stable complex containing MLL1 and MOF has been immunoaffinity purified from a human cell line that stably expresses an epitope-tagged WDR5 subunit [6].
• Stable interactions between MLL1 and MOF were confirmed by reciprocal immunoprecipitation, cosedimentation, and cotransfection analyses, and interaction sites were mapped to MLL1 C-terminal and MOF zinc finger domains [6].
• These results indicate an activator-based mechanism for joint MLL1 and MOF recruitment and targeted methylation and acetylation and provide a molecular explanation for the closely correlated distribution of H3 K4 methylation and H4 K16 acetylation on active genes [6].
• In this issue of Molecular Cell, two manuscripts () propose that the decision to undergo apoptosis upon DNA damage is mediated through acetylation of p53 within its DNA-binding domain by MYST histone acetyltransferases [7].

Chemical compound and disease context of MYST1

• Sequential hemofiltration in MOF associated with paracetamol intoxication and gram-negative sepsis [8].
• Although patients with poor outcomes (i.e., BS, ARDS, MOF, and death) had significantly lower tryptophan levels and greater lymphopenia on several days after injury, the sample size was too small to draw any definitive conclusions [9].
• Metastatic colorectal carcinoma. A prospective randomized trial of Methyl-CCNU, 5-Fluorouracil (5-FU) and vincristine (MOF) versus MOF plus streptozotocin (MOF-Strep) [10].
• A prospective randomized trial evaluated semustine (Methyl CCNU) 5-Fluorouracil (5-FU) and vincristine (MOF) versus MOF plus streptozotocin (MOF-Strep) in 75 patients with advanced, measurable colorectal carcinoma [10].
• Sixty-seven patients with measurable colorectal carcinoma were randomized to receive two different schedules of Methyl CCNU, 5-FU and Vincristine (MOF) [11].

Biological context of MYST1

• In addition, decreased hMOF activity was associated with loss of the cell cycle checkpoint response to DNA double-strand breaks [12].
• The overexpression of wild-type hMOF yielded the opposite results, i.e., a modest increase in cell survival and enhanced DNA repair after IR exposure [12].
• hMOF histone acetyltransferase is required for histone H4 lysine 16 acetylation in mammalian cells [13].
• Reduction of hMOF protein levels by RNA interference in HeLa cells also leads to accumulation of cells in the G(2) and M phases of the cell cycle [13].
• The MYST acetyltransferase HBO1 is implicated in the regulation of DNA replication and activities of transcription factors such as the androgen receptor [14].

Anatomical context of MYST1

• Neutrophil adhesion molecules and MOF [15].
• In conclusion, administration of GHRP-6, given alone or in combination with EGF to enhance its effects, may provide a novel simple approach for the prevention and treatment of MOF and other injuries of the gastrointestinal tract [16].
• The disruption of the blood-brain barrier progresses to the systemic cytokine storm, resulting in DIC and MOF [17].
• Only after such comprehensive studies have been performed, it might be concluded that--as in the experimental animal--sepsis and MOF may not necessarily be caused by bacteria or their endotoxins, but by an untoward autodestructive and self-sustaining activation of angry leucocytes and mad macrophages [18].
• Plasma levels of granulocyte elastase and neopterin in patients with MOF [19].

Associations of MYST1 with chemical compounds

• Male patients who received 5-FU plus LV demonstrated a statistically significant benefit in disease-free survival at 5 years compared with those who received MOF (55% versus 47%; P =.009) but not in 5-year overall survival (65% versus 62%; P =.17) [20].
• The patients were randomized to receive no further treatment (184 patients), postoperative adjuvant chemotherapy with 5-fluorouracil, semustine, and vincristine (MOF) (187 patients), or postoperative radiation therapy (184 patients) [1].
• Here, using the prototypical MYST family member Esa1, and its physiological complex (piccolo NuA4), steady-state kinetic analyses revealed a kinetic mechanism that requires the formation of a ternary complex prior to catalysis, where acetyl-CoA binds first and CoA is the last product released [21].
• Furthermore, in plasma and lymph of four SIRS/MOF patients, a novel cholesterol-containing high-density lipoprotein-like particle was found that barely had LPS binding capacity (<5%) [22].
• CONCLUSIONS: In the SIRS/MOF patients, the changes in lipoprotein composition in lymph are a reflection of those in plasma, except for the triglyceride levels [22].

Physical interactions of MYST1

• Androgen receptor interacts with a novel MYST protein, HBO1 [23].

Regulatory relationships of MYST1

• These results suggest that hMOF influences the function of ATM [12].

Other interactions of MYST1

• Involvement of human MOF in ATM function [12].
• Conversely, the MYST acetylase domain specifically enhanced SRC-1 coupling with PR NTD, through a hormone-dependent mechanism [24].

Analytical, diagnostic and therapeutic context of MYST1

• Knockdown of hMOF in HeLa and HepG2 cells causes a dramatic reduction of histone H4K16 acetylation as detected by Western blot analysis and mass spectrometric analysis of endogenous histones [13].
• MOF as control arm for NSABP adjuvant chemotherapy trial [25].
• All female patients (n = 287) received 5-FU plus LV chemotherapy; male patients received either MOF (n = 207) or 5-FU plus LV (n = 200) [20].
• At 3 years of follow-up, patients treated with postoperative LV + 5-FU had a 30% reduction in the risk of developing a treatment failure and a 32% reduction in mortality risk compared with similar patients treated with MOF [26].
• ABM may provide a synthetic, analytical platform to integrate basic science data on the IIR, thus eventually aiding in formulating and testing future mediator-directed therapies for SIRS/MOF before clinical trials, and it may provide insights into directions of future research [27].

References