TP53 exon-6 truncating mutations produce separation of function isoforms with pro-tumorigenic functions

TP53 truncating mutations are common in human tumors and are thought to give rise to p53-null alleles. Here, we show that TP53 exon-6 truncating mutations occur at higher than expected frequencies and produce proteins that lack canonical p53 tumor suppressor activities but promote cancer cell proliferation, survival, and metastasis. Functionally and molecularly, these p53 mutants resemble the naturally occurring alternative p53 splice variant, p53-psi. Accordingly, these mutants can localize to mitochondria where they promote tumor phenotypes by binding and activating the mitochondria inner pore permeability regulator, Cyclophilin D (CypD). Together, our studies reveal that TP53 exon-6 truncating mutations, contrary to current beliefs, act beyond p53 loss to promote tumorigenesis, and could inform the development of strategies to target cancers driven by these prevalent mutations

Tritium kinetic isotope effects on enzymatic decomposition of L-tryptophan

The tritium kinetic isotope effect on position 2 has been determined in the reaction of decomposition of L-tryptophan, L-Trp, catalyzed by enzyme TPase, (EC 4.1.99.1). The numerical values of isotope effects in the course of reaction were obtained by the competitive method using [1-14C]-L-tryptophan as internal radiometric standard

Long-term talus flatirons formation in the hyperarid northeastern Negev, Israel

Colluvial sediments of talus relicts (“talus flatirons”) around mesas preserve a record that sheds light on slope-forming processes at temporal scales >103 yr. The sedimentology and soil stratigraphy of two groups of talus flatirons in the northeastern hyperarid Negev desert reveal four deposition events in the younger talus and at least two in the older one. Numerical modeling of high-resolution 10Be depth profiles suggests that these taluses were deposited during the middle Pleistocene; the younger talus group first depositional event occurred at 551 −142 +80 ka and its abandonment occurred at 270 −38 +17 ka. The abandonment of the older talus group and stabilization of its surface occurred at 497 −114 +176 ka. These ages indicate that the development of the studied talus sequence is not specifically associated with Pleistocene glacial–interglacial cycles. The 10Be modeled concentrations indicate significant differences in the average inheritance of talus flatirons of different groups. These differences can be attributed to variability in the transport distance and duration of gravel exposure during transport but could also reflect some temporal variability in cliff retreat. Our results also demonstrate that talus slopes in hyperarid areas, despite their steepness, can store sediment for long periods (~500 ka) and thus constitute a valuable archive