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Frank Uhlmann

Publications and source records attributed to Frank Uhlmann.

23 records · Page 2Linked to original sources
PubMed2003

Separase regulation during mitosis.

The final, irreversible step in the duplication and distribution of genomes to daughter cells takes place when chromosomes split at the metaphase-to-anaphase transition. A protease of the CD clan, separase (C50 family), is the key regulator of this transition. During metaphase, cohesion between sister chromatids is maintained by a chromosomal protein complex, cohesin. Anaphase is triggered when separase cleaves the Scc1 subunit of cohesin at two specific recognition sequences. As a result of this cleavage, the cohesin complex is destroyed, allowing the spindle to pull sister chromatids into opposite halves of the cell. Because of the final and irreversible nature of Scc1 cleavage, this reaction is tightly controlled. Several independent mechanisms impose regulation on separase activity, as well as on the susceptibility of the cleavage target Scc1 to cleavage by separase. This chapter provides an overview of these multiple levels of regulation.

Cell Cycle Proteins↗
PubMed2003

Postembolic spectral patterns of Doppler microembolic signals.

OBJECTIVES: This study was performed to examine the prevalence of postembolic spectral patterns in patients with prosthetic heart valves and evaluate their potential relation to the underlying embolic material. METHODS: The prevalence of the tail (TS) and lambda (LS) signs was examined in artifact signals and microembolic signals (MES) detected in 10 patients with prosthetic heart valves and 13 further patients with artificial heart valves during normobaria as well as during hyperbaric exposure (2.5 and 1.75 bar). RESULTS: A total of 1,721 MES were detected in the 10 patients; prevalence of TS and LS were 11 and 9.8%, respectively. Hyperbaric exposure in the second group of patients resulted in a significant increase of the prevalence of LS (13.7% at 2.5 bar and 9.2% at 1.75 bar, as compared to 7.7 and 8.2% during normobaria), while the prevalence of TS remained unchanged, ranging between 5 and 6.7%. Neither TS nor LS was observed following artifact signals. CONCLUSIONS: TS and LS showed a high specificity (100%) but low sensitivity (ranging between 7.7 and 11 and 5 and 9.8%, respectively) for the detection of MES. LS appear to be--at least partially--associated with gaseous embolic material.

Adult↗
PubMed2002

The dual mechanism of separase regulation by securin.

BACKGROUND: Sister chromatid separation and segregation at anaphase onset are triggered by cleavage of the chromosomal cohesin complex by the protease separase. Separase is regulated by its binding partner securin in two ways: securin is required to support separase activity in anaphase; and, at the same time, securin must be destroyed via ubiquitylation before separase becomes active. The molecular mechanisms underlying this dual regulation of separase by securin are unknown. RESULTS: We show that, in budding yeast, securin supports separase localization. Separase enters the nucleus independently of securin, but securin is required and sufficient to cause accumulation of separase in the nucleus, where its known cleavage targets reside. Securin also ensures that separase gains full proteolytic activity in anaphase. We also show that securin, while present, directly inhibits the proteolytic activity of separase. Securin prevents the binding of separase to its substrates. It also hinders the separase N terminus from interacting with and possibly inducing an activating conformational change at the protease active site 150 kDa downstream at the protein's C terminus. CONCLUSIONS: Securin inhibits the proteolytic activity of separase in a 2-fold manner. While inhibiting separase, securin is able to promote nuclear accumulation of separase and help separase to become fully activated after securin's own destruction at anaphase onset.

Binding Sites↗
PubMed2002

Chromosome segregation: playing polo in prophase.

During mitosis, in most eukaryotes, cohesin is removed from chromosomes in two steps. A paper in the March issue of Molecular Cell identifies Polo-like kinase as a key regulator for the first step that releases much of cohesin during prophase.

Animals↗