Yuan JY (1997) Reprod Toxicol "Genetic control of cellular suicide."

Yuan JY

[Reprod Toxicol, 1997]

Genetic analysis of programmed cell death in C. elegans has led to the identification of two genes, ced-9, a cell death suppressor, and ced-3, a cell death inducer, that play critical roles in regulating programmed cell death. The ced-9 and ced-3 genes were found to encode proteins that share structural and functional similarities with the mammalian proto-oncogene product Bcl-2 and interleukin-1 beta converting enzyme (ICE), respectively. Multiple members of the Bcl-2 family and the ICE family have been identified in vertebrates. These results suggest that the mechanism of apoptosis in vertebrates may be evolved from a much simpler version of a similar pathway in primitive organisms.

Yuan S et al. (2013) Structure "Apoptosome structure, assembly, and procaspase activation."

Yuan S, Akey CW

[Structure, 2013]

Apaf-1-like molecules assemble into a ring-like platform known as the apoptosome. This cell death platform then activates procaspases in the intrinsic cell death pathway. In this review, crystal structures of Apaf-1 monomers and CED-4 dimers have been combined with apoptosome structures to provide insights into the assembly of cell death platforms in humans, nematodes, and flies. In humans, the caspase recognition domains (CARDs) of procaspase-9 and Apaf-1 interact with each other to form a CARD-CARD disk, which interacts with the platform to create an asymmetric proteolysis machine. The disk tethers multiple pc-9 catalytic domains to the platform to raise their local concentration, and this leads to zymogen activation. These findings have now set the stage for further studies of this critical activation process on the apoptosome.

Yuan J et al. (2010) Genes Dev "Alternative cell death mechanisms in development and beyond."

Kroemer G, Yuan J

[Genes Dev, 2010]

A canonical regulatory pathway involving the members of the Bcl-2 and caspase families has been established to regulate developmental apoptosis in nematodes and flies. However, mutant mice that have major deficiencies in this apoptosis pathway show only relatively minor developmental defects. Recent revelations indicate that multiple mechanisms are involved in regulating cell death during mammalian development, tissue homeostasis, and pathological cell loss. Here, we critically evaluate the evidence demonstrating the existence of alternative cell death mechanisms, including apoptosis of lower organisms in the absence of canonical apoptosis mediators, autophagic cell death, necroptosis, elimination by shedding, keratinocyte death by cornification, and cell-cell cannibalism by entosis. The physiological relevance of alternative cell death mechanisms as primary and backup mechanisms is discussed.

Yuan JY (1995) Curr Opin Cell Biol "Molecular control of life and death."

Yuan JY

[Curr Opin Cell Biol, 1995]

Recent evidence has shown that two of the three key genes in the programmed cell death pathway of Caenorhabditis elegans, ced-9 (a cell death suppressor) and ced-3 (a cell death inducer), encode proteins that share structural and functional similarities with the mammalian proto-oncogene product Bcl-2 and interleukin-1 beta converting enzyme, respectively. These findings reveal key molecules that control lire and death decisions in vertebrates.

Yuan JY (1996) J Cell Biochem "Evolutionary conservation of a genetic pathway of programmed cell death."

Yuan JY

[J Cell Biochem, 1996]

Genetic analysis of programmed cell death in Caenorhabditis elegans has led to the identification of 13 genes that constitute a developmental pathway of programmed cell death. Two of the three key genes in this pathway, ced-9, a cell death suppressor, and ced-3, a cell death inducer, were found to encode proteins that share structural and functional similarities with the mammalian proto-oncogene product Bcl-2 and interleukin-1 beta converting enzyme, respectively. These results suggest that the genetic pathway of programmed cell death may be evolutionarily conserved from worms to mammals.

Hodgkin JA (1998) International Journal of Developmental Biology "Seven types of pleiotropy."

Hodgkin JA

[International Journal of Developmental Biology, 1998]

Pleiotropy , a situation in which a single gene influences multiple phenotypic tra its, can arise in a variety of ways. This paper discusses possible underlying mechanisms and proposes a classification of the various phenomena involved.

Wong C et al. (2003) Curr Biol "Dispatch. Centrosome biology: a SAS-sy centriole in the cell cycle."

Wong C, Stearns T

[Curr Biol, 2003]

A novel protein in Caenorhabditis elegans, SAS-4, is a component of centrioles and is required for centriole duplication. Depletion of SAS-4 results in stunted centrioles and a smaller centrosome, suggesting a link to organelle size control.

Hall PA et al. (1997) Curr Biol "Tumor suppressors: a developing role for p53?"

Hall PA, Lane DP

[Curr Biol, 1997]

An increasing body of evidence indicates that p53, the product of a tumour suppressor gene, has a role in development - could this developmental role have provided the primary driving force in the evolution of a protein best known as a stress-response integrator?

Smidt MP et al. (2009) Genome Biol "A passport to neurotransmitter identity."

Burbach JP, Smidt MP

[Genome Biol, 2009]

Comparison of a regulatory network that specifies dopaminergic neurons in Caenorhabditis elegans to the development of vertebrate dopamine systems in the mouse reveals a possible partial conservation of such a network.

Bourne HR et al. (1990) Nature "Some signal developments."

Kenyon CJ, Bourne HR, Wrischnik LA

[Nature, 1990]

What molecular signalling machines tell a precursor cell to develop into a specialized structure? In one case, described in three papers, including that by Aroian et al. on page 693 of this issue, these machines turn out to be a receptor tyrosine kinase and a ras protein.