Long lifetime and tissue-specific accumulation of lamin A/C in Hutchinson-Gilford progeria syndrome.

LMNA mutations cause laminopathies that afflict the cardiovascular system and include Hutchinson-Gilford progeria syndrome. The origins of tissue specificity in these diseases are unclear as the lamin A/C proteins are broadly expressed. We show that LMNA transcript levels are not predictive of lamin A/C protein levels across tissues and use quantitative proteomics to discover that tissue context and disease mutation each influence lamin A/C protein's lifetime.

Long lifetime and selective accumulation of the A-type lamins accounts for the tissue specificity of Hutchinson-Gilford progeria syndrome.

Mutations to the gene cause laminopathies including Hutchinson-Gilford progeria syndrome (HGPS) that severely affect the cardiovascular system. The origins of tissue specificity in these diseases are unclear, as the A-type Lamins are abundant and broadly expressed proteins. We show that A-type Lamin protein and transcript levels are uncorrelated across tissues.

Turnover and replication analysis by isotope labeling (TRAIL) reveals the influence of tissue context on protein and organelle lifetimes.

The lifespans of proteins range from minutes to years within mammalian tissues. Protein lifespan is relevant to organismal aging, as long-lived proteins accrue damage over time. It is unclear how protein lifetime is shaped by tissue context, where both cell turnover and proteolytic degradation contribute to protein turnover.

Transcriptional Repression of SIRT3 Potentiates Mitochondrial Aconitase Activation to Drive Aggressive Prostate Cancer to the Bone.

Metabolic dysregulation is a known hallmark of cancer progression, yet the oncogenic signals that promote metabolic adaptations to drive metastatic cancer remain unclear. Here, we show that transcriptional repression of mitochondrial deacetylase sirtuin 3 () by androgen receptor (AR) and its coregulator steroid receptor coactivator-2 (SRC-2) enhances mitochondrial aconitase (ACO2) activity to favor aggressive prostate cancer. ACO2 promoted mitochondrial citrate synthesis to facilitate lipogenesis, and genetic ablation of reduced total lipid content and severely repressed prostate cancer progression.

Fine structure of the pygmy dipole resonance in (136)Xe.

The photoresponse of the semimagic N=82 nucleus (136)Xe was measured up to the neutron separation energy S(n) using the (gamma, gamma') reaction. A concentration of strong dipole excitations is observed well below S(n) showing a fragmented resonancelike structure. Microscopic calculations in the quasiparticle phonon model including complex configurations of up to three phonons agree well with the experimental data in the total integrated strength, in the shape and the fragmentation of the resonance, which allows us to draw conclusions on the damping mechanism of the pygmy dipole resonance.