%0 Journal Article
%T Period-2: a tumor suppressor gene in breast cancer
%A Shulin Xiang
%A Seth B Coffelt
%A Lulu Mao
%A Lin Yuan
%A Qi Cheng
%A Steven M Hill
%J Journal of Circadian Rhythms
%D 2008
%I BioMed Central
%R 10.1186/1740-3391-6-4
%X In mammals, most body functions follow a rhythmic pattern adjusted to a 24 h period (circadian rhythm), which is controlled by the circadian timing system [1,2]. Circadian rhythmicity is an evolutionarily conserved property that regulates numerous functions in the human body including sleep and wakefulness, body temperature, blood pressure, hormone production, digestive secretion, and immune activity [3]. The circadian timing system comprises peripheral oscillators located in most tissues of the body and a central rhythm generator located in the suprachiasmatic nucleus (SCN) of the hypothalamus [4]. The SCN pacemaker consists of multiple, autonomous single cell circadian oscillators, which are synchronized to fire rhythmically, generating a coordinated, rhythmic output in intact animals [5,6].The cellular mechanism of circadian rhythmicity involves the regulation of three Period genes (Per 1¨C3) and two Chrytochrome genes (Cry1 and 2) [4]. Currently, it is thought that transcription of Per and Cry genes is driven by accumulating CLOCK:BMAL1 heterodimers, which in turn bind to consensus E-box elements [7-10]. Subsequently, complexes of PER 2 and CRY 2 proteins enter the nucleus, where they shut off CLOCK-mediated transcription. At the same time, PER 2 up-regulates the levels of BMAL1 mRNA leading to the formation of CLOCK:BMAL1 heterodimers, which drive Per 2 and Cry 2 transcription and restart the cycle [11,12]. MOP4 (member of the PAS superfamily 4), also named NPAS2, shares high homology with CLOCK [13] and like CLOCK forms a heterodimer with BMAL1, promoting E-box activation of genes such as Per1 and vasopressin and is negatively regulated by CRY 1 and 2 [11]. In adult animals, oscillatory expression of CLOCK genes has been demonstrated in the SCN and in several peripheral tissues. Interacting positive and negative transcriptional-translational feedback loops drive circadian oscillators in both Drosphila and mammals. Furthermore, immortalized rat fibroblasts harbo
%U http://www.jcircadianrhythms.com/content/6/1/4