Sp1転写因子

Sp1転写因子（specificity protein 1）は、ヒトではSP1遺伝子によってコードされるタンパク質である。 SP1遺伝子にコードされるSP1タンパク質はジンクフィンガー型転写因子であり、多くのプロモーターのGCリッチモチーフに結合する。SP1タンパク質は、細胞分化、細胞成長、アポトーシス、免疫応答、DNA損傷応答、クロマチンリモデリングなど多くの細胞過程に関与している。このタンパク質の活性はリン酸化、アセチル化、グリコシル化などの翻訳後修飾やタンパク質分解によるプロセシングの影響を受け、アクチベーターとしてもリプレッサーとしても機能する。 ミトコンドリアフェリチン遺伝子（FTMT）の推定プロモーター領域に結合する転写の正の調節因子としてSP1、CREB、YY1が、負の調節因子としてGATA2（英語版）、FOXA1（英語版）、C/EBPβ（英語版）が同定されている。これらの調節因子のDNA結合活性に対するデフェリプロン（英語版）（DFP）の影響がクロマチン免疫沈降（ChIP）アッセイによって調べられている。これらの中で、SP1のみがDFP処理後に用量依存的なDNA結合活性の大幅な増大を示した。siRNAによるSP1のノックダウンによってDFPによるFTMTのｍRNAレベルの増加はみられなくなることから、DFPの存在下ではSP1を介したFTMTの発現の調節が行われていることが示唆される。DFP処理はSP1の細胞質および核内での発現を増加させ、主に核内に局在させる。 SP1は転写因子のSp/KLFファミリー（英語版）に属し、785アミノ酸長、81 kDaである。SP1転写因子はジンクフィンガーモチーフをもち、これを介してDNAに直接結合して遺伝子の転写を亢進させる。ジンクフィンガーはCys2/His2型で、5'-(G/T)GGGCGG(G/A)(G/A)(C/T)-3'のコンセンサス配列（GCボックス（英語版）エレメント）に結合する。ヒトゲノム中には12,000か所程度のSP1結合部位が見つかっている。 Sp1は芳香族炭化水素受容体やエストロゲン受容体の双方に結合し、そして比較的一定のレベルで存在するため、これらの受容体の増加や減少の研究の際のコントロールタンパク質として利用される。 Streptomyces plicatus（英語版）によって産生される抗腫瘍性抗生物質であるプリカマイシン（英語版）や、アシュワガンダWithania somnifera由来のステロイドラクトンであるウィザフェリンA（英語版）はSp1転写因子を阻害することが知られている。 miR-375-5pは大腸がん細胞でSP1とYAP1の発現を大きく低下させる。SP1とYAP1のｍRNAはmiR-375-5pの直接的な標的である。 Sp1転写因子は次に挙げる因子と相互作用することが示されている。 AATF（英語版） CEBPB（英語版） COL1A1（英語版） E2F1（英語版） FOSL1（英語版） GABPA（英語版） HDAC1（英語版） HDAC2（英語版） HMGA1（英語版） HCFC1（英語版） HTT KLF6（英語版） MEF2C（英語版） MEF2D（英語版） MSX1（英語版） MYOG（英語版） POU2F1（英語版） PPP1R13L（英語版） PSMC5（英語版） PML RELA（英語版） SMAD3 SUMO1（英語版） SF1（英語版） TAL1（英語版） UBC（英語版） WRN ^ a b c GRCh38: Ensembl release 89: ENSG00000185591 - Ensembl, May 2017 ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000001280 - Ensembl, May 2017 ^ Human PubMed Reference: ^ Mouse PubMed Reference: ^ a b “Entrez Gene: Sp1 transcription factor”. 2021年10月3日閲覧。 ^ Guaraldo, Michela; Santambrogio, Paolo; Rovelli, Elisabetta; Di Savino, Augusta; Saglio, Giuseppe; Cittaro, Davide; Roetto, Antonella; Levi, Sonia (2016-09-14). “Characterization of human mitochondrial ferritin promoter: identification of transcription factors and evidences of epigenetic control”. 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PMID 18258854.  Sp1 Transcription Factor - MeSH・アメリカ国立医学図書館・生命科学用語シソーラス（英語） FactorBook SP1