Fumarate hydratase inactivation in renal tumors: HIF1α, NRF2, and "cryptic targets" of transcription factors / 癌症
Chinese Journal of Cancer
;
(12): 413-420, 2012.
Article
in English
| WPRIM
| ID: wpr-295859
ABSTRACT
Biallelic inactivation of fumarate hydratase(FH) causes type 2 papillary renal cell carcinoma (PRCC2), uterine fibroids, and cutaneous leimyomas, a condition known as hereditary leiomyomatosis and renal cell cancer(HLRCC). The most direct effect of FH inactivation is intracellular fumarate accumulation. A majority of studies on FH inactivation over the past decade have focused on the theory that intracellular fumarate stabilizes hypoxia-inducible factor 1α(HIF1A) through competitive inhibition of HIF prolyl hydroxylases. Recently, a competing theory that intracellular fumarate activates nuclear factor (erythroid-derived 2)-like 2(NRF2) through post-translational modification of its negative regulator. Kelch-like ECH-associated protein 1(KEAP1) has emerged from a computational modeling study and mouse model studies. This review dissects the origin of these two governing theories and highlights the presence of chromatin-structure-regulated targets of transcription factors, which we refer to as "cryptic targets" of transcription factors. One such cryptic target is heme oxygenase I(HMOX1), the expression of which is known to be modulated by the gene product of SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4, also known as BRG1).
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Skin Neoplasms
/
Transcription Factors
/
Uterine Neoplasms
/
Neoplastic Syndromes, Hereditary
/
Nuclear Proteins
/
Protein Processing, Post-Translational
/
Leiomyomatosis
/
DNA Helicases
/
Procollagen-Proline Dioxygenase
/
Intracellular Signaling Peptides and Proteins
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
Chinese Journal of Cancer
Year:
2012
Type:
Article
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