A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells.

By D. Kwiatkowski, Hongbing Zhang, Jennifer L. Bandura, Kristina M Heiberger, M. Glogauer, N. el-Hashemite, H. Onda. Human Molecular Genetics, 2002

700 citations recorded by the source corpus.

Subfields: Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/4d84c864caddca8e8af1d5ee08138caa2a9ee0eb

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Citations in the corpus

Dysregulation of the TSC-mTOR pathway in human disease (2004, unknown): “In TSC1 −/− , TSC2 −/− or PTEN −/− cells, phosphorylation of both S6K and 4EBP1 is hig”
Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome. (2004, background): “The best-characterized cellular function of TSC2 is to inhibit the phosphorylation of the translational regulators S6K and 4EBP1 (Goncharova et al. 2002; Inoki et al. 2002; Kwiatkowski et al. 2002).”
Akt stimulates hepatic SREBP1c and lipogenesis through parallel mTORC1-dependent and independent pathways (2011, methodology): “To delete Tsc1 specifically in hepatocytes, we used a previously described floxed allele of Tsc1 (Tsc1) (Figure 2A) (Kwiatkowski et al., 2002), backcrossed onto a pure C57BL/6J background.”
The LKB1 tumor suppressor negatively regulates mTOR signaling. (2004, background): “Similarly, as seen previously (Kwiatkowski et al., 2002; Jaeschke et al., 2002), Akt activity is dramatically attenuated in the Tsc2deficient cells following all stimuli, a phenomenon which has previously been attributed to a negative feedback loop inhibiting PI3K/Akt signaling in a number of system”
Defining the role of mTOR in cancer. (2007, background): “For example, loss of TSC1/2 function results in decreased AKT phosphorylation (Jaeschke et al., 2002; Kwiatkowski et al., 2002).”
Ras superfamily GEFs and GAPs: validated and tractable targets for cancer therapy? (2010, background): “Although the tumour phenotype is distinct, the increased incidence of renal cell carcinoma and other cancers in Eker rats, which have germline heterozygous Tsc2 mutations that inactivate the RHEBGAP activity of tuberin, supports the role of TSC2 as a tumour suppresso”
A complex interplay between Akt, TSC2, and the two mTOR complexes (2009, background): “However, attenuation of growth-factor stimulated Akt phosphorylation is seen more generally upon disruption of the TSC1-TSC2 complex, such as under full serum growth conditions [27,28,31], where the IRS proteins should play only a minor role.”
Activation of a metabolic gene regulatory network downstream of mTOR complex 1. (2010, background): “The use of both Tsc1 and Tsc2 null cells provides an added degree of stringency and controls for nonspecific differences in these independently derived lines (Kwiatkowski et al., 2002; Zhang et al., 2003).”
Autistic-like behavior and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice (2012, unknown): “To evaluate Tsc1 's role in cerebellar PCs, we generated mice with Tsc1 deleted in cerebellar PCs ( L7 Cre ;Tsc1 flox/+ (het) or L7 Cre ;Tsc1 flox/flox (mutant)) 10 .”
Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models (2011, background): “Akt1+Akt2 null Neonatal lethality Severe growth retardation (birth weight 50% of control), marked muscle atrophy [77] TSC1 null Embryonic lethality [ 126 ]”
Upstream and downstream of mTOR. (2004, background): “This situation is similar to that in TSC2 null cells, in which mTOR is constitutively activated (Jaeschke et al. 2002; Kwiatkowski et al. 2002; Zhang et al. 2003a).”
TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling (2002, unknown): “Consistently, an enhancement of S6K phosphorylation has been observed in TSC1 null cell”
Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. (2004, background): “In support of the idea that Tsc1/Tsc2 plays a critical role in mTOR regulation by growth factors, cells deficient for Tsc1 or Tsc2 fail to down-regulate mTOR function in response to growth factor deprivation (Gao et al. 2002; Inoki et al. 2002; Jaeschke et al. 2002; Kwiatkowski et al. 2002; H. Zhang”
The TSC1-TSC2 complex: a molecular switchboard controlling cell growth. (2008, background): “rapamycin-sensitive) phosphorylation of both S6K1 and 4E-BP1 is inhibited by TSC1–TSC2 complex overexpression and is activated in cells lacking the TSC1–TSC2 complex [21,22,25,42–45].”