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181.
Kank proteins: structure, functions and diseases 总被引:1,自引:1,他引:0
N. Kakinuma Y. Zhu Y. Wang B. C. Roy R. Kiyama 《Cellular and molecular life sciences : CMLS》2009,66(16):2651-2659
The Kank family of proteins, Kank1–Kank4, are characterized by their unique structure, coiled-coil motifs in the N-terminal
region, and ankyrin-repeats in the C-terminal region, with an additional motif, the KN motif, at the N-terminus. Kank1 was obtained by positional cloning of a tumor suppressor gene in renal cell carcinoma, while the other members were found
by homology search. The family is involved in the regulation of actin polymerization and cell motility through signaling pathways
containing PI3K/Akt and/or unidentified modulators/effectors. Their relationship to diseases such as cancer, and to neuronal
and developmental disorders, will be an important subject of future study. 相似文献
182.
Inhibiting the production of amyloid-β by antagonising γ-secretase activity is currently being pursued as a therapeutic strategy
for Alzheimer’s disease (AD). However, early pre-clinical studies have demonstrated that disruption of presenilin-dependent
γ-secretase alters many presenilin-dependent processes, leading to early lethality in several AD model organisms. Subsequently,
transgenic animal studies have highlighted several gross developmental side effects arising from presenilin deficiency. Partial
knockdown or tissue-specific knockout of presenilins has identified the skin, vascular and immune systems as very sensitive
to loss of presenilin functions. A more appreciative understanding of presenilin biology is therefore demanded if γ-secretase
is to be pursued as a therapeutic target. Herein we review the current understanding of γ-secretase complexes; their regulation,
abundance of interacting partners and diversity of substrates. We also discuss regulation of the γ-secretase complexes, with
an emphasis on the functional role of presenilins in cell biology.
Received 25 July 2008; received after revision 24 November 2008; accepted 10 December 2008 相似文献
183.
ROPs in the spotlight of plant signal transduction 总被引:7,自引:0,他引:7
Berken A 《Cellular and molecular life sciences : CMLS》2006,63(21):2446-2459
Small guanine nucleotide binding proteins of the Rho family called ROP play a crucial role as regulators of signal transduction
in plants. They participate in pathways that influence growth and development, and the adaptation of plants to various environmental
situations. As members of the Ras superfamily, ROPs function as molecular switches cycling between a GDP-bound ‘off’ and a
GTP-bound ‘on’ state in a strictly regulated manner. Latest research provided fascinating new insights into ROP regulation
by novel guanine nucleotide exchange factors, unconventional GTPase activating proteins, and guanine nucleotide dissociation
inhibitors, which apparently organize localized ROP activation. Important progress has also been made concerning signaling
components upstream and downstream of the ROP cycle involving receptor-like serine/threonine kinases and effectors that can
manipulate cytoskeletal dynamics, intracellular calcium levels, H2O2 production and further cellular targets. This review outlines the fast developing knowledge on ROP GTPases highlighting their
specific features, regulation and roles in a cellular signaling context.
Received 28 April 2006; received after revision 2 June 2006; accepted 29 June 2006 相似文献
184.
Benton R 《Cellular and molecular life sciences : CMLS》2006,63(14):1579-1585
Olfaction, the sense of smell, depends on large, divergent families of odorant receptors that detect odour stimuli in the
nose and transform them into patterns of neuronal activity that are recognised in the brain. The olfactory circuits in mammals
and insects display striking similarities in their sensory physiology and neuroanatomy, which has suggested that odours are
perceived by a conserved mechanism. Here I review recent revelations of significant structural and functional differences
between the Drosophila and mammalian odorant receptor proteins and discuss the implications for our understanding of the evolutionary
and molecular biology of the insect odorant receptors.
Received 23 March 2006; accepted 28 April 2006 相似文献
185.
UV-B和NO对胞壁蛋白的影响 总被引:7,自引:0,他引:7
通过对玉米幼苗叶片细胞壁中蛋白组分、质量分数和过氧化物酶活性的分析检测,证明UV-B光胁迫下,内、外源NO作为UV-B辐射光氧化胁迫的信使负责胁迫信号的转导,激活细胞壁过氧化物酶的活性,致使细胞壁共价键结合蛋白,积累,从而钝化许多功能蛋白质的活力.而没有UV-B光胁迫时,适量的内、外源NO是抑制细胞壁过氧化物酶活性的有效抗胁迫分子,保证细胞壁中足量离子结合和游离蛋白质量分数,维持细胞壁中活跃的代谢功能.因此,在细胞壁中,一氧化氮能够介导UV-B辐射对细胞壁中结构和功能蛋白质的影响,为转导增强UV-B光胁迫的信号分子. 相似文献
186.
Smrcka AV 《Cellular and molecular life sciences : CMLS》2008,65(14):2191-2214
G protein betagamma subunits are central participants in G protein-coupled receptor signaling pathways. They interact with receptors, G protein alpha subunits and downstream targets to coordinate multiple, different GPCR functions. Much is known about the biology of Gbetagamma subunits but mysteries remain. Here, we will review what is known about general aspects of structure and function of Gbetagamma as well as discuss emerging mechanisms for regulation of Gbetagamma signaling. Recent data suggest that Gbetagamma is a potential therapeutic drug target. Thus, a thorough understanding of the molecular and physiological functions of Gbetagamma has significant implications. 相似文献
187.
Terpenoids: natural inhibitors of NF-κB signaling with anti-inflammatory and anticancer potential 总被引:1,自引:0,他引:1
Salminen A Lehtonen M Suuronen T Kaarniranta K Huuskonen J 《Cellular and molecular life sciences : CMLS》2008,65(19):2979-2999
Traditional medicine has been a fertile source for revealing novel lead molecules for modern drug discovery. In plants, terpenoids
represent a chemical defense against environmental stress and provide a repair mechanism for wounds and injuries. Interestingly,
effective ingredients in several plant-derived medicinal extracts are also terpenoid compounds of monoterpenoid, sesquiterpenoid,
diterpenoid, triterpenoid and carotenoid groups. Inflammatory diseases and cancer are typical therapeutic indications of traditional
medicines. Thus folk medicine supports the studies which have demonstrated that plant-derived terpenoid ingredients can suppress
nuclear factor-κB (NF-κB) signaling, the major regulator in the pathogenesis of inflammatory diseases and cancer.We review
the extensive literature on the different types of terpenoid molecules, totalling 43, which have been verified both inhibiting
the NF-κB signaling and suppressing the process of inflammation and cancer. It seems that during evolution, plants have established
a terpene-based host defense which also represents a cornucopia of effective therapeutic compounds for common human diseases.
Received 11 March 2008; received after revision 28 April 2008; accepted 29 April 2008 相似文献
188.
189.
190.
Mitogenic signals stimulate cell division by activating cyclin/cyclin-dependent kinase (CDK) complexes. Their timely regulation
ensures proper cell cycle progression. It is therefore not surprising that cyclin/CDK complexes are integrators of multiple
signals from both the extracellular environment and intracellular cues. Important regulators of cyclin/CDKs are the CDK inhibitors
that have attracted attention due to their association with disease. p27KIP1 is a CDK inhibitor that controls CDK activity throughout the cell cycle. As a CDK inhibitor, p27KIP1 has tumor suppressor activity. Besides CDKs, p27KIP1 regulates additional cellular processes, including cell motility, some of which seem to mediate oncogenic activities of p27KIP1. These activities of p27KIP1 are regulated through multiple phosphorylation sites, targeted by several signal transduction pathways. Understanding functions
and regulation of p27KIP1 will be important to determine which isoform of p27KIP1 has anti- or pro-tumorigenic activities. Such knowledge might be of prognostic value and may offer novel therapeutic windows.
Received 26 May 2008; accepted 17 June 2008 相似文献