The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3

Zhang, Jun; Yang, Jinbo; Roy, Sitikantha; Tininini, Silvia; Hu, Jiadi; Bromberg, Jacqueline; Poli, Valeria; Stark, George R.; Kalvakolanu, Dhananjaya V.

doi:10.1073/pnas.1633516100

Cited by 155 publications

(167 citation statements)

References 44 publications

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“…We have begun collecting more tumor tissues to address these questions. We and others have recently shown that GRIM-19 binds to STAT3 and inhibits its gene stimulating functions (Lufei et al, 2003;Zhang et al, 2003). In this regard, GRIM-19 appears to behave like the VHL protein, which binds to transcription factor HIF1 and prevents its gene stimulatory function (Iliopoulos et al, 1996;Maxwell et al, 1999).…”

Section: Discussionmentioning

confidence: 94%

“…In the CycB1-Luc constrct, the luciferase reporter is driven by the cyclin B1 promoter (Katula et al, 1997). Transfection and luciferase reporter analysis and WB analyses were performed as described earlier Zhang et al, 2003). Cell growth assays were performed using a colorimetric assay based on the use of sulforhodamine B (Skehan et al, 1990) as described in our earlier studies .…”

Section: Methodsmentioning

confidence: 99%

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A proteomic analysis reveals the loss of expression of the cell death regulatory gene GRIM-19 in human renal cell carcinomas

et al. 2006

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Section: Discussionmentioning

confidence: 94%

Section: Methodsmentioning

confidence: 99%

A proteomic analysis reveals the loss of expression of the cell death regulatory gene GRIM-19 in human renal cell carcinomas

et al. 2006

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“…Although their functions are mostly unknown, one subunit, NDUFAB1, is an acyl carrier protein (34); NDUFA9 is related to steroid dehydrogenases (35); NDUFA13 is reported to regulate cell growth and apoptosis (36); and NDUFA2 has a thioredoxin fold (37) and is a component of the membrane region of subcomplex Iα. Human mutations in it result in leukodystrophy (17), and as shown here, it is required for the assembly and/or possibly the structural integrity of complex I.…”

Section: Discussionmentioning

confidence: 99%

Assembly factors for the membrane arm of human complex I

Andrews

Carroll

Ding

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

129

125

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Mitochondrial respiratory complex I is a product of both the nuclear and mitochondrial genomes. The integration of seven subunits encoded in mitochondrial DNA into the inner membrane, their association with 14 nuclear-encoded membrane subunits, the construction of the extrinsic arm from 23 additional nuclear-encoded proteins, iron-sulfur clusters, and flavin mononucleotide cofactor require the participation of assembly factors. Some are intrinsic to the complex, whereas others participate transiently. The suppression of the expression of the NDUFA11 subunit of complex I disrupted the assembly of the complex, and subcomplexes with masses of 550 and 815 kDa accumulated. Eight of the known extrinsic assembly factors plus a hydrophobic protein, C3orf1, were associated with the subcomplexes. The characteristics of C3orf1, of another assembly factor, TMEM126B, and of NDUFA11 suggest that they all participate in constructing the membrane arm of complex I. mitochondria | respiratory chain | NADH:ubiquinone oxidoreductase

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“…One such growth inhibitor was GRIM-19, a protein whose depletion and overexpression, respectively, promoted and suppressed tumor growth (13). GRIM-19 binds to STAT3 and inhibits its transcriptional activity (14,15). Additionally, we and others have shown that GRIM-19 expression is lost in several primary tumors of lung, kidney, prostate, thyroid, ovary, colon, esophagus, and brain.…”

mentioning

confidence: 99%

Monoallelic loss of tumor suppressor GRIM-19 promotes tumorigenesis in mice

Kalakonda¹,

Nallar²,

Jaber

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Significance Gene-associated with retinoid-interferon induced mortality-19 (GRIM-19) is an interferon-retinoid–regulated growth suppressor that inhibits cell growth by targeting the transcription factor STAT3 for inhibition. In primary human tumors GRIM-19 is suppressed or mutated, leading to constitutive STAT3 activity and indicating the tumor-suppressive function of GRIM-19. To understand the in vivo role of Grim-19 in tumor development, we generated a Grim-19 conditional knockout mouse. We found that deletion of even a single Grim-19 allele is sufficient to augment skin tumorigenesis in mice, thus establishing a critical role for Grim-19 as a tumor suppressor. Tumors that developed in the absence of Grim-19 exhibited mitochondrial respiratory chain dysfunction, elevated glycolysis, and Stat3-responsive gene expression.

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The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3

Cited by 155 publications

References 44 publications

A proteomic analysis reveals the loss of expression of the cell death regulatory gene GRIM-19 in human renal cell carcinomas

A proteomic analysis reveals the loss of expression of the cell death regulatory gene GRIM-19 in human renal cell carcinomas

Assembly factors for the membrane arm of human complex I

Monoallelic loss of tumor suppressor GRIM-19 promotes tumorigenesis in mice

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