IRGQ-mediated autophagy in MHC class I quality control promotes tumor immune evasion

被引：11

作者：

Herhaus, Lina ^{[1
]}

Gestal-Mato, Uxia ^{[1
]}

Eapen, Vinay V. ^{[2
,3
]}

Macinkovic, Igor ^{[1
,4
]}

Bailey, Henry J. ^{[1
,5
]}

Prieto-Garcia, Cristian ^{[1
]}

Misra, Mohit ^{[1
,5
]}

Jacomin, Anne-Claire ^{[1
]}

Ammanath, Aparna Viswanathan ^{[1
]}

Bagaric, Ivan ^{[1
]}

Michaelis, Jolina ^{[1
]}

Vollrath, Joshua ^{[1
,5
,6
]}

Bhaskara, Ramachandra M. ^{[1
,5
]}

Buendgen, Georg ^{[7
]}

Covarrubias-Pinto, Adriana ^{[1
]}

Husnjak, Koraljka ^{[1
]}

Zoeller, Jonathan ^{[6
]}

Gikandi, Ajami ^{[2
]}

Ribicic, Sara ^{[1
]}

Bopp, Tobias ^{[7
]}

van Noort, Gerbrand J. van der Heden ^{[8
]}

Langer, Julian D. ^{[6
]}

Weigert, Andreas ^{[4
]}

Harper, J. Wade ^{[3
]}

Mancias, Joseph D. ^{[2
]}

Dikic, Ivan ^{[1
,5
,6
]}

机构：

[1] Goethe Univ Frankfurt, Inst Biochem 2, Med Fac, Theodor Stern Kai 7, D-60590 Frankfurt, Germany

[2] Harvard Inst Med, Dana Farber Canc Inst, Dept Radiat Oncol, Div Radiat & Genome Stabil, 450 Brookline Ave, Boston, MA 02215 USA

[3] Harvard Med Sch, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA

[4] Goethe Univ, Inst Biochem 1, Sch Med, Theodor Stern Kai 7, D-60590 Frankfurt, Germany

[5] Goethe Univ Frankfurt, Buchmann Inst Mol Life Sci, Riedberg Campus,Max von Laue Str 15, D-60438 Frankfurt, Germany

[6] Goethe Univ Frankfurt, Max Planck Inst Biophys, Riedberg Campus, D-60438 Frankfurt, Germany

[7] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Immunol, Mainz, Germany

[8] Leiden Univ, Med Ctr, Dept Cell & Chem Biol, Leiden, Netherlands

来源：

CELL | 2024年 / 187卷 / 25期

关键词：

PROTEIN; CANCER; DEGRADATION; HOMEOSTASIS; EXPRESSION; MOLECULES; MECHANISM; DYNAMICS; MODELS; EFFLUX;

D O I：

10.1016/j.cell.2024.09.048

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The autophagy-lysosome system directs the degradation of a wide variety of cargo and is also involved in tumor progression. Here, we show that the immunity-related GTPase family Q protein (IRGQ), an uncharacterized protein to date, acts in the quality control of major histocompatibility complex class I (MHC class I) molecules. IRGQ directs misfolded MHC class I toward lysosomal degradation through its binding mode to GABARAPL2 and LC3B. In the absence of IRGQ, free MHC class I heavy chains do not only accumulate in the cell but are also transported to the cell surface, thereby promoting an immune response. Mice and human patients suffering from hepatocellular carcinoma show improved survival rates with reduced IRGQ levels due to increased reactivity of CD8+ T cells toward IRGQ knockout tumor cells. Thus, we reveal IRGQ as a regulator of MHC class I quality control, mediating tumor immune evasion.

引用

页码：7285 / 7302.e29

页数：48

共 93 条

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