At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, how...

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Free Radicals in the Physiological Control of Cell Function

The pUC plasmids, an M13mp7-derived system for insertion mutagenesis and sequencing with synthetic universal primers.

Mitogen-activated protein (MAP) kinases comprise a family of ubiquitous proline-directed, protein-serine/threonine kinases, which participate in signal transduction pathways that control intracellular events including acute responses to hormones and major developmental changes in organisms. MAP kinases lie in protein kinase cascades. This review discusses the regulation and functions of mammalian MAP kinases. Nonenzymatic mechanisms that impact MAP kinase functions and findings from gene disruption studies are highlighted. Particular emphasis is on ERK1/2.

/pdf/mitogen-activated-protein-map-kinase-pathways-regulation-and-3nsauvepr2.pdf

Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions.

The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

https://biblio.ugent.be/publication/8555786/file/8555788.pdf

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

https://www.cell.com/cell/pdf/0092-8674(93)90383-2.pdf

MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo

We have previously identified by cDNA cloning 5 mRNAs that appear in resting BALB/c 3T3 cells soon after growth stimulation by serum or platelet-derived growth factor. Five additional mRNAs of this class are described in this report. The mRNAs reached peak levels between 40 and 120 min after serum addition and rapidly decayed thereafter. All 10 RNAs were superinduced in the presence of cycloheximide. Nuclear run-on experiments indicated that the increase in the mRNAs is the result of rapid transcriptional activation of their genes on stimulation by serum or platelet-derived growth factor. Superinducibility by cycloheximide is due to two effects: prolonged transcription and stabilization of mRNAs. This overall pattern of regulation is similar to that of the c-fos or c-myc protooncogenes reported previously. We hypothesize that these newly identified "immediate early" genes play a role in the proliferative response induced by growth factors.

https://www.pnas.org/content/pnas/84/5/1182.full.pdf

Expression of a set of growth-related immediate early genes in BALB/c 3T3 cells: coordinate regulation with c-fos or c-myc

Cellular senescence is a recognized mechanism of tumour suppression; however, its contribution to other pathologies is not well understood. We show that the matricellular protein CCN1 (also known as CYR61; cysteine-rich protein 61), which is dynamically expressed at sites of wound repair, can induce fibroblast senescence by binding to integrin alpha(6)beta(1) and the heparan sulphate proteoglycans (receptors involved in cell adhesion). CCN1 induces DNA damage response pathways and activates p53 and the RAC1-NOX1 complex, which generates reactive oxygen species (ROS). This results in the ROS-dependent activation of the p16(INK4a)/pRb pathway, leading to senescence and concomitant expression of antifibrotic genes. Senescent fibroblasts accumulate in granulation tissues of healing cutaneous wounds and express antifibrotic genes in wild-type mice. These processes are lost in knockin mice that express a senescence-defective Ccn1 mutant, resulting in exacerbated fibrosis. Topical application of CCN1 protein to wounds reverses these defects. Thus, fibroblast senescence is a CCN1-dependent wound healing response in cutaneous injury that functions to curb fibrosis during tissue repair.

/pdf/the-matricellular-protein-ccn1-induces-fibroblast-senescence-3sox8vtt8q.pdf

The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing

Exposure of mammalian cells to DNA-damaging agents leads to activation of a genetic response known as the UV response. Because several previously identified UV-inducible genes contain AP-1 binding sites within their promoters, we investigated the induction of AP-1 activity by DNA-damaging agents. We found that expression of both c-jun and c-fos, which encode proteins that participate in formation of the AP-1 complex, is rapidly induced by two different DNA-damaging agents: UV and H2O2. Interestingly, the c-jun gene is far more responsive to UV than any other immediate-early gene that was examined, including c-fos. Other jun and fos genes were only marginally affected by UV or H2O2. Furthermore, UV is a much more efficient inducer of c-jun than phorbol esters, the standard inducers of c-jun expression. This preferential response of the c-jun gene is mediated by its 5' control region and requires the TPA response element, suggesting that this element also serves as an early target for the signal transduction pathway elicited by DNA damage. Both UV and H2O2 lead to a long-lasting increase in AP-1 binding activity, suggesting that AP-1 may mediate the induction of other damage-inducible genes such as human collagenase.

Lester F. Lau

Papers

MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo

Expression of a set of growth-related immediate early genes in BALB/c 3T3 cells: coordinate regulation with c-fos or c-myc

The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing

Rapid and preferential activation of the c-jun gene during the mammalian UV response.

The CCN family of angiogenic regulators: the integrin connection.