Uncontrolled cell proliferation is the hallmark of cancer, and tumor cells have typically acquired damage to genes that directly regulate their cell cycles. Genetic alterations affecting p16(INK4a) and cyclin D1, proteins that govern phosphorylation of the retinoblastoma protein (RB) and control exit from the G1 phase of the cell cycle, are so frequent in human cancers that inactivation of this pathway may well be necessary for tumor development. Like the tumor suppressor protein p53, components of this "RB pathway," although not essential for the cell cycle per se, may participate in checkpoint functions that regulate homeostatic tissue renewal throughout life.

http://science.sciencemag.org/content/sci/274/5293/1672.full.pdf

Cancer Cell Cycles

The retinoblastoma protein and cell cycle control

/pdf/inhibitors-of-mammalian-g1-cyclin-dependent-kinases-38eef2u6ay.pdf

Inhibitors of mammalian G1 cyclin-dependent kinases.

Multiple genetic changes occur during the evolution of normal cells into cancer cells. This evolution is facilitated in cancer cells by loss of fidelity in the processes that replicate, repair, and segregate the genome. Recent advances in our understanding of the cell cycle reveal how fidelity is normally achieved by the coordinated activity of cyclin-dependent kinases, checkpoint controls, and repair pathways and how this fidelity can be abrogated by specific genetic changes. These insights suggest molecular mechanisms for cellular transformation and may help to identify potential targets for improved cancer therapies.

https://science.sciencemag.org/content/sci/266/5192/1821.full.pdf

Cell cycle control and cancer

https://www.cell.com/cell/pdf/0092-8674(94)90572-X.pdf

Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals

CYTOGENETIC abnormalities of chromosome 9p21 are characteristic of malignant melanomas1,2, gliomas3, lung cancers4 and leukaemias5. From a panel of 46 human malignant cell lines, we localized by positional cloning the most frequently deleted region on 9p21. Sequence analysis of the isolated fragment reveals two open reading frames identical to the recently described complementary DNA for the inhibitor of cyclin-dependent kinase 4 (CDK4) 6. Polymerase chain reaction and Southern blot analysis confirmed the frequent deletion or rearrangement of the CDK4-inhibitor gene in melanomas, gliomas, lung cancers and leukaemias, and the absence of detectable gene transcripts. One carcinoma had a deletion entirely within the CDK4-inhibitor gene. The CDK4-inhibitor gene from a patient with dysplastic nevus syndrome had a germ-line nonsense mutation. The CDK4 inhibitor is thought to be a physiological suppressor of proliferation. Cells unable to produce the inhibitor may be prone to neoplastic transformation.

Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers

Regulation of expression of the casbene synthetase gene during elicitation of castor bean seedlings with pectic fragments.

Most fungal and bacterial plant pathogens can establish systemic infections in a very limited range of host plants Thus, higher plants in general are able to resist infection by most of the fungal and bacterial phytopathogens they may encounter In cases of general resistance during the interaction of a non-host plant with a microbial pathogen, no obvious symptoms develop in the plant During other cases of interaction of a non-host plant, or resistant cultivars of a host plant, with a microbial pathogen, a limited necrotic lesion develops rapidly in the host plant after penetration of the microbe This hypersensitive response is characterized by the rapid death of one or more plant cells at the site of microbial invasion, and the induction of production in still healthy plant cells immediately surrounding this site of a number of new metabolic products1

Augusto F. Lois

Papers

Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers

Regulation of expression of the casbene synthetase gene during elicitation of castor bean seedlings with pectic fragments.

Diterpenoid phytoalexins: biosynthesis and regulation.