RICTOR

RICTOR
معین‌کننده‌ها
نام‌های دیگر	RICTOR, AVO3, PIA, hAVO3, RPTOR independent companion of MTOR complex 2
شناسه‌های بیرونی	OMIM: 609022 MGI: 1926007 HomoloGene: 34317 GeneCards: RICTOR
موقعیت ژن (موش)
کروموزوم	کروموزوم ۱۵ (موش)
پایان	6,829,882 bp
الگوی گسترش RNA
	More reference expression data
هستی‌شناسی ژن
عملکرد ملکولی	• ribosome binding; • GO:0001948، GO:0016582 پیوند پروتئینی; • GO:0010577 enzyme activator activity; • protein kinase binding;
ترکیبات سلولی	• سیتوزول; • TORC2 complex;
فرایند زیستی	• regulation of protein phosphorylation; • actin cytoskeleton reorganization; • positive regulation of protein kinase B signaling; • positive regulation of endothelial cell proliferation; • positive regulation of actin filament polymerization; • regulation of actin cytoskeleton organization; • embryo development; • GO:0043087، GO:0032313، GO:0032319، GO:0032314، GO:0043088 regulation of GTPase activity; • regulation of phosphorylation; • establishment or maintenance of actin cytoskeleton polarity; • multicellular organism development; • TOR signaling; • GO:0035404 peptidyl-serine phosphorylation; • regulation of peptidyl-serine phosphorylation; • regulation of protein kinase B signaling; • establishment of cell polarity; • regulation of inflammatory response; • positive regulation of peptidyl-tyrosine phosphorylation; • ساماندهی بیان ژن; • regulation of establishment of cell polarity; • positive regulation of TOR signaling; • activation of protein kinase B activity; • embryo development ending in birth or egg hatching; • GO:0022415 viral process;
	منابع: آمیگو / کوئیک‌گو
هم‌ساخت‌شناسی
	253260
	78757
	ENSG00000164327
	ENSMUSG00000050310
	Q6R327
	Q6QI06
	NM_001285440، NM_152756، XM_006714463، XM_011514005، XM_011514006، XM_017009311، XM_017009312، XM_047417068، XM_047417069، XM_047417070 NM_001285439، NM_001285440، NM_152756، XM_006714463، XM_011514005، XM_011514006، XM_017009311، XM_017009312، XM_047417068، XM_047417069، XM_047417070
	XM_006520003، XM_036159639، XR_004938879 NM_030168، XM_006520003، XM_036159639، XR_004938879
	NP_001272369، NP_689969، XP_006714526، XP_011512307، XP_011512308، XP_016864800، XP_016864801، XP_016864802، XP_016864803، XP_016864804 NP_001272368، NP_001272369، NP_689969، XP_006714526، XP_011512307، XP_011512308، XP_016864800، XP_016864801، XP_016864802، XP_016864803، XP_016864804
	XP_006520066، XP_036015532 NP_084444، XP_006520066، XP_036015532
	ویکی‌داده
مشاهده/ویرایش انسان	مشاهده/ویرایش موش

مولکولِ کمکیِ غیر حساس به راپامایسین از مولکولِ هدفِ راپامایسین پستانداران (انگلیسی: Rapamycin-insensitive companion of mammalian target of rapamycin) که بیشتر با نام اختصاری «RICTOR» شناخته می‌شود، یک پروتئین است که در انسان توسط ژن «RICTOR» کُدگذاری می‌شود.^[۴]^[۵] این ژن بر روی بازوی کوتاه کروموزوم ۵ قرار دارد و طول آن ۵۴۴۰ جفت‌باز است.^[۶]^[۷] جایگاه T1135 در این ژن توسط فاکتورهای رشد و طریق پی۷۰-اس۶ کیناز ۱ فسفریله می‌شود.^[۸]

RICTOR و MTOR اجزای یک مجموعهٔ ترکیبیِ پروتئینی هستند که سیگنال‌های مشتق از مواد مغذی و فاکتور رشد را برای تنظیم رشد سلولی هماهنگ و یکپارچه می‌کند.^[۵] در واقع این مولکول یکی از بخش‌های مجموعهٔ ترکیبیِ mTORC2 است که سایر اجزای آنرا mTOR, GβL و mSIN1 تشکیل می‌دهند.^[۹] مشخص شده‌است که mTORC2 و RICTOR به کمک هم Akt/PKB را در جایگاه سرین۴۷۳ فسفریله می‌کنند. بهم خوردن تنظیم Akt/PKB در بروز در سرطان و دیابت نقش دارد.^[۱۰]

mTORC2 و RICTOR همچنین نقش مهمی در رشد و تکامل جنینی دارند؛ چرا که mTORC2 بر روی سامان‌دهی ساختار اکتین اثر می‌گذارد.^[۱۱]

فاکتورهای رونویسی FoxO بیان ژن «RICTOR» را تحریک می‌کنند. در واقع FoxO پروتئین mTORC1 را مهار می‌کند اما با فعال سازی پروتئین کیناز بی سبب افزایش RICTOR می‌شوند.^[۱۲] پریفوسین سبب تجزیهٔ RICTOR می‌گردد.^[۱۳]

اهمیت بالینی

جهش در ژن «RICTOR» با بروز مننژیومای سوراخ بزرگ پس‌سری و سیرنگومیلی در ارتباط است. فعال شدن پروتئین کیناز بی توسط RICTOR در سوخت‌وساز کربوهیدرات و چربی‌ها و بروز دیابت نوع ۲ نقش دارد.^[۱۴]

این پروتئین به‌طور غیرمستقیم در بروز برخی سرطان‌ها نقش دارد؛ از جمله سرطان روده بزرگ،^[۱۵] گلیوبلاستوما،^[۱۶] لیومیوسارکوما^[۱۷] و آدنوم هیپوفیز.^[۱۸]

منابع

↑ ^۱٫۰ ^۱٫۱ ^۱٫۲ GRCm38: Ensembl release 89: ENSMUSG00000050310 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Marra MA (Dec 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc Natl Acad Sci U S A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
↑ ^۵٫۰ ^۵٫۱ "Entrez Gene: RICTOR rapamycin-insensitive companion of mTOR".
↑ "Gene & protein Summary: RICTOR". EMBL-EBI.
↑ "Homo sapiens rapamycin-insensitive companion of mTOR, mRNA (cDNA clone IMAGE:5787163), partial cds". UniGene.
↑ Dibble CC, Asara JM, Manning BD (2009). "Characterization of RICTOR phosphorylation sites reveals direct regulation of mTOR complex 2 by S6K1". Mol. Cell. Biol. 29 (21): 5657–70. doi:10.1128/MCB.00735-09. PMC 2772744. PMID 19720745.
↑ Sarbassov DD, Ali SM, Kim DH, Guertin DA, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM (2004). "RICTOR, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton". Curr. Biol. 14 (14): 1296–302. doi:10.1016/j.cub.2004.06.054. PMID 15268862. S2CID 4658268.
↑ Sarbassov DD, Guertin DA, Ali SM, Sabatini DM (2005). "Phosphorylation and regulation of Akt/PKB by the RICTOR-mTOR complex". Science. 307 (5712): 1098–101. Bibcode:2005Sci...307.1098S. doi:10.1126/science.1106148. PMID 15718470. S2CID 45837814.
↑ Shiota C, Woo JT, Lindner J, Shelton KD, Magnuson MA (2006). "Multiallelic disruption of the gene RICTOR in mice reveals that mTOR complex 2 is essential for fetal growth and viability". Dev. Cell. 11 (4): 583–9. doi:10.1016/j.devcel.2006.08.013. PMID 16962829.
↑ Chen CC, Jeon SM, Bhaskar PT, Nogueira V, Sundararajan D, Tonic I, Park Y, Hay N (2010). "FoxOs inhibit mTORC1 and activate Akt by inducing the expression of Sestrin3 and RICTOR". Dev. Cell. 18 (4): 592–604. doi:10.1016/j.devcel.2010.03.008. PMC 3031984. PMID 20412774.
↑ Fu L, Kim YA, Wang X, Wu X, Yue P, Lonial S, Khuri FR, Sun SY (2009). "Perifosine inhibits mammalian target of rapamycin signaling through facilitating degradation of major components in the mTOR axis and induces autophagy". Cancer Res. 69 (23): 8967–76. doi:10.1158/0008-5472.CAN-09-2190. PMC 2789206. PMID 19920197.
↑ Kumar A, Lawrence JC, Jung DY, Ko HJ, Keller SR, Kim JK, Magnuson MA, Harris TE (2010). "Fat cell-specific ablation of rictor in mice impairs insulin-regulated fat cell and whole-body glucose and lipid metabolism". Diabetes. 59 (6): 1397–406. doi:10.2337/db09-1061. PMC 2874700. PMID 20332342.
↑ Guo Z, Zhou Y, Evers BM, Wang Q (2012). "RICTOR regulates FBXW7-dependent c-Myc and cyclin E degradation in colorectal cancer cells". Biochem. Biophys. Res. Commun. 418 (2): 426–32. doi:10.1016/j.bbrc.2012.01.054. PMC 3278531. PMID 22285861.
↑ Verreault M, Weppler SA, Stegeman A, Warburton C, Strutt D, Masin D, Bally MB (2013). "Combined RNAi-mediated suppression of RICTOR and EGFR resulted in complete tumor regression in an orthotopic glioblastoma tumor model". PLOS ONE. 8 (3): e59597. Bibcode:2013PLoSO...859597V. doi:10.1371/journal.pone.0059597. PMC 3598699. PMID 23555046.
↑ Gibault L, Ferreira C, Pérot G, Audebourg A, Chibon F, Bonnin S, Lagarde P, Vacher-Lavenu MC, Terrier P, Coindre JM, Aurias A (2012). "From PTEN loss of expression to RICTOR role in smooth muscle differentiation: complex involvement of the mTOR pathway in leiomyosarcomas and pleomorphic sarcomas". Mod. Pathol. 25 (2): 197–211. doi:10.1038/modpathol.2011.163. PMID 22080063.
↑ Jia W, Sanders AJ, Jia G, Liu X, Lu R, Jiang WG (August 2013). "Expression of the mTOR pathway regulators in human pituitary adenomas indicates the clinical course". Anticancer Res. 33 (8): 3123–31. PMID 23898069.

برای مطالعهٔ بیشتر

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Sarbassov DD, Ali SM, Kim DH, et al. (2004). "Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton". Curr. Biol. 14 (14): 1296–302. doi:10.1016/j.cub.2004.06.054. PMID 15268862. S2CID 4658268.
Beausoleil SA, Jedrychowski M, Schwartz D, et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
Jacinto E, Loewith R, Schmidt A, et al. (2004). "Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive". Nat. Cell Biol. 6 (11): 1122–8. doi:10.1038/ncb1183. PMID 15467718. S2CID 13831153.
Kudchodkar SB, Yu Y, Maguire TG, Alwine JC (2006). "Human cytomegalovirus infection alters the substrate specificities and rapamycin sensitivities of raptor- and rictor-containing complexes". Proc. Natl. Acad. Sci. U.S.A. 103 (38): 14182–7. Bibcode:2006PNAS..10314182K. doi:10.1073/pnas.0605825103. PMC 1599931. PMID 16959881.
Jacinto E, Facchinetti V, Liu D, et al. (2006). "SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity". Cell. 127 (1): 125–37. doi:10.1016/j.cell.2006.08.033. PMID 16962653. S2CID 230319.
Yang Q, Inoki K, Ikenoue T, Guan KL (2006). "Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activity". Genes Dev. 20 (20): 2820–32. doi:10.1101/gad.1461206. PMC 1619946. PMID 17043309.
Fuchs BC, Finger RE, Onan MC, Bode BP (2007). "ASCT2 silencing regulates mammalian target-of-rapamycin growth and survival signaling in human hepatoma cells". Am. J. Physiol., Cell Physiol. 293 (1): C55–63. doi:10.1152/ajpcell.00330.2006. PMID 17329400.
Pearce LR, Huang X, Boudeau J, et al. (2007). "Identification of Protor as a novel Rictor-binding component of mTOR complex-2". Biochem. J. 405 (3): 513–22. doi:10.1042/BJ20070540. PMC 2267312. PMID 17461779.

[refGRCm38Ensembl-1] ۱٫۰ ^۱٫۱ ^۱٫۲ GRCm38: Ensembl release 89: ENSMUSG00000050310 - Ensembl, May 2017

[2] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[3] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid_12477932-4] Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Marra MA (Dec 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc Natl Acad Sci U S A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.

[entrez-5] ۵٫۰ ^۵٫۱ "Entrez Gene: RICTOR rapamycin-insensitive companion of mTOR".

[urlGene_&_protein_Summary:_RICTOR-6] "Gene & protein Summary: RICTOR". EMBL-EBI.

[urlUniGene-7] "Homo sapiens rapamycin-insensitive companion of mTOR, mRNA (cDNA clone IMAGE:5787163), partial cds". UniGene.

[pmid_19720745-8] Dibble CC, Asara JM, Manning BD (2009). "Characterization of RICTOR phosphorylation sites reveals direct regulation of mTOR complex 2 by S6K1". Mol. Cell. Biol. 29 (21): 5657–70. doi:10.1128/MCB.00735-09. PMC 2772744. PMID 19720745.

[pmid_15268862-9] Sarbassov DD, Ali SM, Kim DH, Guertin DA, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM (2004). "RICTOR, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton". Curr. Biol. 14 (14): 1296–302. doi:10.1016/j.cub.2004.06.054. PMID 15268862. S2CID 4658268.

[pmid_15718470-10] Sarbassov DD, Guertin DA, Ali SM, Sabatini DM (2005). "Phosphorylation and regulation of Akt/PKB by the RICTOR-mTOR complex". Science. 307 (5712): 1098–101. Bibcode:2005Sci...307.1098S. doi:10.1126/science.1106148. PMID 15718470. S2CID 45837814.

[pmid_16962829-11] Shiota C, Woo JT, Lindner J, Shelton KD, Magnuson MA (2006). "Multiallelic disruption of the gene RICTOR in mice reveals that mTOR complex 2 is essential for fetal growth and viability". Dev. Cell. 11 (4): 583–9. doi:10.1016/j.devcel.2006.08.013. PMID 16962829.

[pmid_20412774-12] Chen CC, Jeon SM, Bhaskar PT, Nogueira V, Sundararajan D, Tonic I, Park Y, Hay N (2010). "FoxOs inhibit mTORC1 and activate Akt by inducing the expression of Sestrin3 and RICTOR". Dev. Cell. 18 (4): 592–604. doi:10.1016/j.devcel.2010.03.008. PMC 3031984. PMID 20412774.

[pmid_19920197-13] Fu L, Kim YA, Wang X, Wu X, Yue P, Lonial S, Khuri FR, Sun SY (2009). "Perifosine inhibits mammalian target of rapamycin signaling through facilitating degradation of major components in the mTOR axis and induces autophagy". Cancer Res. 69 (23): 8967–76. doi:10.1158/0008-5472.CAN-09-2190. PMC 2789206. PMID 19920197.

[pmid_20332342-14] Kumar A, Lawrence JC, Jung DY, Ko HJ, Keller SR, Kim JK, Magnuson MA, Harris TE (2010). "Fat cell-specific ablation of rictor in mice impairs insulin-regulated fat cell and whole-body glucose and lipid metabolism". Diabetes. 59 (6): 1397–406. doi:10.2337/db09-1061. PMC 2874700. PMID 20332342.

[pmid_22285861-15] Guo Z, Zhou Y, Evers BM, Wang Q (2012). "RICTOR regulates FBXW7-dependent c-Myc and cyclin E degradation in colorectal cancer cells". Biochem. Biophys. Res. Commun. 418 (2): 426–32. doi:10.1016/j.bbrc.2012.01.054. PMC 3278531. PMID 22285861.

[pmid_23555046-16] Verreault M, Weppler SA, Stegeman A, Warburton C, Strutt D, Masin D, Bally MB (2013). "Combined RNAi-mediated suppression of RICTOR and EGFR resulted in complete tumor regression in an orthotopic glioblastoma tumor model". PLOS ONE. 8 (3): e59597. Bibcode:2013PLoSO...859597V. doi:10.1371/journal.pone.0059597. PMC 3598699. PMID 23555046.

[pmid_22080063-17] Gibault L, Ferreira C, Pérot G, Audebourg A, Chibon F, Bonnin S, Lagarde P, Vacher-Lavenu MC, Terrier P, Coindre JM, Aurias A (2012). "From PTEN loss of expression to RICTOR role in smooth muscle differentiation: complex involvement of the mTOR pathway in leiomyosarcomas and pleomorphic sarcomas". Mod. Pathol. 25 (2): 197–211. doi:10.1038/modpathol.2011.163. PMID 22080063.

[pmid_23898069-18] Jia W, Sanders AJ, Jia G, Liu X, Lu R, Jiang WG (August 2013). "Expression of the mTOR pathway regulators in human pituitary adenomas indicates the clinical course". Anticancer Res. 33 (8): 3123–31. PMID 23898069.

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