Abstract：
:Autophagy is crucial for cellular homeostasis and plays important roles in tumorigenesis. FIP200 (FAK family-interacting protein of 200 kDa) is an essential autophagy gene required for autophagy induction, functioning in the ULK1-ATG13-FIP200 complex. Our previous studies showed that conditional knockout of FIP200 significantly suppressed mammary tumorigenesis, which was accompanied by accumulation of p62 in tumor cells. However, it is not clear whether FIP200 is also required for maintaining tumor growth and how the increased p62 level affects the growth in autophagy-deficient FIP200-null tumors in vivo. Here, we describe a new system to delete FIP200 in transformed mouse embryonic fibroblasts as well as mammary tumor cells following their transplantation and show that ablation of FIP200 significantly reduced growth of established tumors in vivo. Using similar strategies, we further showed that either p62 knockdown or p62 deficiency in established FIP200-null tumors dramatically impaired tumor growth. The stimulation of tumor growth by p62 accumulation in FIP200-null tumors is associated with the up-regulated activation of the NF-κB pathway by p62. Last, we showed that overexpression of the autophagy master regulator TFEB(S142A) increased the growth of established tumors, which correlated with the increased autophagy of the tumor cells. Together, our studies demonstrate that p62 and autophagy synergize to promote tumor growth, suggesting that inhibition of both pathways could be more effective than targeting either alone for cancer therapy.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Wei H,Wang C,Croce CM,Guan JLdoi
10.1101/gad.237354.113subject
Has Abstractpub_date
2014-06-01 00:00:00pages
1204-16issue
11eissn
0890-9369issn
1549-5477pii
28/11/1204journal_volume
28pub_type
杂志文章abstract：:Several previously known transcription cofactors have been demonstrated in vitro recently to be histone acetyltransferases and deacetyltransferases, suggesting that remodeling of chromatin through histone acetylation plays a fundamental role in gene regulation. Clear evidence has not yet been obtained, however, to dem...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.12.5.640
更新日期：1998-03-01 00:00:00
abstract：:Eukaryotic RNAs with premature termination codons (PTCs) are eliminated by nonsense-mediated decay (NMD). While human nonsense RNA degradation can be initiated either by an endonucleolytic cleavage event near the PTC or through decapping, the individual contribution of these activities on endogenous substrates has rem...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.246538.114
更新日期：2014-11-15 00:00:00
abstract：:Protein kinases are key regulators of cellular processes. In spite of considerable effort, a full understanding of the pathways they participate in remains elusive. We globally investigated the proteins that interact with the majority of yeast protein kinases using protein microarrays. Eighty-five kinases were purifie...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1998811
更新日期：2011-04-01 00:00:00
abstract：:Hepatitis B virus (HBV) infects humans and causes a wide range of clinical manifestations, from acute hepatitis to hepatocellular carcinoma (HCC). The HBV genome contains multiple promoters with gene expression regulated predominantly by the cellular transcription initiation machinery. Accordingly, the HBV-encoded pX,...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.12.8.1217
更新日期：1998-04-15 00:00:00
abstract：:To determine the prevalence of cotranscriptional splicing in Drosophila, we sequenced nascent RNA transcripts from Drosophila S2 cells as well as from Drosophila heads. Eighty-seven percent of the introns assayed manifest >50% cotranscriptional splicing. The remaining 13% are cotranscriptionally spliced poorly or slow...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.178962.111
更新日期：2011-12-01 00:00:00
abstract：:Pax3 is a key transcription factor implicated in development and human disease. To dissect the role of Pax3 in myogenesis and establish whether it is a repressor or activator, we generated loss- and gain-of-function alleles by targeting an nLacZ reporter and a sequence encoding the oncogenic fusion protein PAX3-FKHR i...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.281203
更新日期：2003-12-01 00:00:00
abstract：:Numerous lines of study have suggested that the Hox genes, encoding putative transcription factors, are key genes in the establishment of the body plan of the mammalian embryo. To examine the role of Hoxa-5 (Hox1.3) gene during development, we have used targeted mutagenesis in embryonic stem cells to produce a strain ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.7.11.2085
更新日期：1993-11-01 00:00:00
abstract：:The tobacco mitogen-activated protein kinase (MAPK) cascade, which includes MAPK NRK1/NTF6, positively regulates expansion of the cytokinetic machinery known as the phragmoplast, which is followed by the synthesis of cell plates for completion of cell division. However, molecular events lying between the MAPK and phra...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1408106
更新日期：2006-04-15 00:00:00
abstract：:The chromo domain was identified as a homologous protein motif between Polycomb (Pc)--a member of the Pc-group genes encoding transcriptional repressors of the homeotic genes--and HP1--a heterochromatin-associated protein encoded by the suppressor of position effect variegation gene Su(var)205. Together with previous ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.6.7.1241
更新日期：1992-07-01 00:00:00
abstract：:Checkpoint genes maintain genomic stability by arresting cells after DNA damage. Many of these genes also control cell cycle events in unperturbed cells. By conducting a screen for checkpoint genes in zebrafish, we found that dtl/cdt2 is an essential component of the early, radiation-induced G2/M checkpoint. We subseq...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1482106
更新日期：2006-11-15 00:00:00
abstract：:One of the central requirements for eukaryotic chromosome stability is the maintenance of the simple sequence tracts at telomeres. In this study, we use genetic and physical assays to reveal the nature of a novel mechanism by which telomere length is controlled. This mechanism, telomeric rapid deletion (TRD), is capab...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.10.11.1310
更新日期：1996-06-01 00:00:00
abstract：:The repression of the maternally inherited Igf2 allele has been proposed to depend on a methylation-sensitive chromatin insulator organized by the 11 zinc finger protein CTCF at the H19 imprinting control region (ICR). Here we document that point mutations of the nucleotides in physical contact with CTCF within the en...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.254903
更新日期：2003-03-01 00:00:00
abstract：:Two recent reports, including one by Reinders and colleagues (pp. 939-950) in the April 15, 2009, issue of Genes & Development, describe the construction of Arabidopsis recombinant inbred populations that maximize epigenetic rather than genetic variation. The distribution and behavior of phenotypic variation in these ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1824909
更新日期：2009-07-15 00:00:00
abstract：:Many short-lived mRNAs, including those encoding lymphokines, cytokines, and proto-oncogenes, contain an AU-rich sequence in their 3'-untranslated regions. These AU domains and, more specifically, AUUUA motifs within them, are widely thought to mediate the extreme instability of the corresponding mRNAs. This is most c...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.6.10.1927
更新日期：1992-10-01 00:00:00
abstract：:The cJun N-terminal kinase 1 (JNK1) is implicated in diet-induced obesity. Indeed, germline ablation of the murine Jnk1 gene prevents diet-induced obesity. Here we demonstrate that selective deficiency of JNK1 in the murine nervous system is sufficient to suppress diet-induced obesity. The failure to increase body mas...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1878510
更新日期：2010-02-01 00:00:00
abstract：:The liver regenerates upon partial hepatectomy (PH) as terminally differentiated hepatocytes undergo a tremendous proliferative process. CREM gene expression is powerfully induced during liver regeneration. We show that cell proliferation is significantly reduced upon PH in CREM-/- mice. There is a reduction in DNA sy...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.12.23.3639
更新日期：1998-12-01 00:00:00
abstract：:Transcription is often stochastic. This is seemingly incompatible with the importance of gene expression during development. Here we show that during zebrafish embryogenesis, transcription activation is stochastic due to (1) genes acquiring transcriptional competence at different times in different cells, (2) differen...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.302935.117
更新日期：2017-08-15 00:00:00
abstract：:Centromeres are maintained epigenetically by the presence of CENP-A, an evolutionarily conserved histone H3 variant, which directs kinetochore assembly and hence centromere function. To identify factors that promote assembly of CENP-A chromatin, we affinity-selected solubilized fission yeast CENP-ACnp1 chromatin. All ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.332536.119
更新日期：2020-02-01 00:00:00
abstract：:Genomic imprinting is an epigenetic process regulated by germline-derived DNA methylation, causing parental origin-specific monoallelic gene expression. Zinc finger protein 57 (ZFP57) is critical for maintenance of this epigenetic memory during post-fertilization reprogramming, yet incomplete penetrance of ZFP57 mutat...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.320069.118
更新日期：2019-01-01 00:00:00
abstract：:O(6)-Methylguanine ((Me)G) is a highly cytotoxic DNA modification generated by S(N)1-type methylating agents. Despite numerous studies implicating DNA replication, mismatch repair (MMR), and homologous recombination (HR) in (Me)G toxicity, its mode of action has remained elusive. We studied the molecular transactions ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.455407
更新日期：2007-12-15 00:00:00
abstract：:The Rbfox proteins (Rbfox1, Rbfox2, and Rbfox3) regulate the alternative splicing of many important neuronal transcripts and have been implicated in a variety of neurological disorders. However, their roles in brain development and function are not well understood, in part due to redundancy in their activities. Here w...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.182477.111
更新日期：2012-03-01 00:00:00
abstract：:Mice mutant for the bHLH gene Hes1, which is known to keep cells in a proliferative state, mostly lack thymus. Transfer of Hes1-null fetal liver cells into RAG2-null host mice normally reconstitutes B cells but fails to generate mature T cells in the thymus. In the reconstituted thymus, T cell differentiation is arres...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.13.9.1203
更新日期：1999-05-01 00:00:00
abstract：:GRF2, an abundant yeast protein of Mr approximately 127,000, binds to the GAL upstream activating sequence (UASG) and creates a nucleosome-free region of approximately 230 bp. Purified GRF2 binds to sequences found in many other UASs, in the 35S rRNA enhancer, at centromeres, and at telomeres. Although GRF2 stimulates...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.4.4.503
更新日期：1990-04-01 00:00:00
abstract：:A prominent feature of cell differentiation is the initiation and maintenance of an irreversible cell cycle arrest with the complex involvement of the retinoblastoma (RB) family (RB, p130, p107). We have isolated the HBP1 transcriptional repressor as a potential target of the RB family in differentiated cells. By homo...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.11.3.383
更新日期：1997-02-01 00:00:00
abstract：:The POU transcription factor Oct-4 is expressed specifically in the germ line, pluripotent cells of the pregastrulation embryo and stem cell lines derived from the early embryo. Osteopontin (OPN) is a protein secreted by cells of the preimplantation embryo and contains a GRGDS motif that can bind to specific integrin ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.12.13.2073
更新日期：1998-07-01 00:00:00
abstract：:Regions on the surface of human TATA-box binding protein (TBP) required for activated transcription in vivo were defined by construction of a library of 89 surface residue mutants with radical substitutions that were assayed for their ability to support activated transcription in vivo, basal transcription in vitro, an...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.10.19.2491
更新日期：1996-10-01 00:00:00
abstract：:The timing of asexual fruiting body formation during Aspergillus nidulans colony development is precisely regulated so that conidiophores are typically produced 1-2 mm behind the growing edge of the colony. Mutations in any of four A. nidulans genes, flbB, flbC, flbD, or flbE, result in colonies that are delayed at le...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.9.4.491
更新日期：1995-02-15 00:00:00
abstract：:Translation of encephalomyocarditis virus (EMCV) mRNA occurs by ribosomal internal entry into the 5'-nontranslated region (5' NTR) rather than by ribosomal scanning. The internal ribosomal entry site (IRES) in the EMCV 5' NTR was determined by in vitro translation with RNAs that were generated by in vitro transcriptio...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.4.9.1560
更新日期：1990-09-01 00:00:00
abstract：:The recombination-activating gene 1 (RAG1) and RAG2 proteins initiate V(D)J recombination, the process that assembles the B- and T-lymphocyte antigen receptor genes of jawed vertebrates. RAG1 and RAG2 are thought to have arisen from a transposable element, but the origins of this element are not understood. We show th...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.278432.116
更新日期：2016-04-15 00:00:00
abstract：:The ability to maintain and expand the pool of adipocytes in adults is integral to the regulation of energy balance, tissue/stem cell homeostasis, and disease pathogenesis. For decades, our knowledge of adipocyte precursors has relied on cellular models. The identity of native adipocyte precursors has remained unclear...
journal_title：Genes & development
pub_type： 杂志文章,评审
doi：10.1101/gad.293704.116
更新日期：2017-01-15 00:00:00
