Papers of note in Nature 548 (7668)

Leslie K. Ferrarelli

doi:10.1126/scisignal.aap7677

This week’s articles describe how the stroma promotes tissue regeneration in the stomach; show how mitosis, the DNA sensor cGAS, and CDK inhibitors contribute to antitumor immunity; and describe the mechanism of action of an allosteric beta blocker.

TISSUE REGENERATION

Stromal support for regeneration

Sigal et al. report that myofibroblast-derived R-spondin 3 promotes regeneration of the stomach epithelium by activating Wnt signaling in Axin2⁺ stem cells.

TUMOR IMMUNOLOGY

cGAS fuels innate immunity

Mackenzie et al. show that the cytoplasmic DNA sensor cGAS detects DNA in ruptured micronuclei and activates an innate immune response to tumors.

Let 'em divide

Harding et al. discover that mitotic progression is critical to the cGAS-mediated inflammatory response to tumors and the efficacy of therapies that combine genotoxic agents with immunotherapy.

CDK4/6 inhibitors are immunostimulatory

Goel et al. show that inhibition of the cell cycle kinases CDK4 and CDK6 not only induces tumor cell cycle arrest but also promotes antitumor immunity by increasing the amount of intracellular double-stranded RNA in tumors and inhibiting the proliferation of regulatory T cells.

STRUCTURAL BIOLOGY

Close-up of a beta blocker

Liu et al. reveal the crystal structure of the β₂ adrenergic receptor in complex with compound 15, an allosteric modulator that binds to an alternative binding pocket.

Highlighted Articles

1. M. Sigal,
2. C. Y. Logan,
3. M. Kapalczynska,
4. H.-J. Mollenkopf,
5. H. Berger,
6. B. Wiedenmann,
7. R. Nusse,
8. M. R. Amieva,
9. T. F. Meyer
, Stromal R-spondin orchestrates gastric epithelial stem cells and gland homeostasis. Nature 548, 451–455 (2017).
OpenUrl
1. K. J. Mackenzie,
2. P. Carroll,
3. C.-A. Martin,
4. O. Murina,
5. A. Fluteau,
6. D. J. Simpson,
7. N. Olova,
8. H. Sutcliffe,
9. J. K. Rainger,
10. A. Leitch,
11. R. T. Osborn,
12. A. P. Wheeler,
13. M. Nowotny,
14. N. Gilbert,
15. T. Chandra,
16. M. A. M. Reijns,
17. A. P. Jackson
, cGAS surveillance of micronuclei links genome instability to innate immunity. Nature 548, 461–465 (2017).
OpenUrl
1. S. M. Harding,
2. J. L. Benci,
3. J. Irianto,
4. D. E. Discher,
5. A. J. Minn,
6. R. A. Greenberg
, Mitotic progression following DNA damage enables pattern recognition within micronuclei. Nature 548, 466–470 (2017).
OpenUrl
1. S. Goel,
2. M. J. DeCristo,
3. A. C. Watt,
4. H. BrinJones,
5. J. Sceneay,
6. B. B. Li,
7. N. Khan,
8. J. M. Ubellacker,
9. S. Xie,
10. O. Metzger-Filho,
11. J. Hoog,
12. M. J. Ellis,
13. C. X. Ma,
14. S. Ramm,
15. I. E. Krop,
16. E. P. Winer,
17. T. M. Roberts,
18. H.-J. Kim,
19. S. S. McAllister,
20. J. J. Zhao
, CDK4/6 inhibition triggers anti-tumour immunity. Nature 548, 471–475 (2017).
OpenUrl
1. X. Liu,
2. S. Ahn,
3. A. W. Kahsai,
4. K.-C. Meng,
5. N. R. Latorraca,
6. B. Pani,
7. A. J. Venkatakrishnan,
8. A. Masoudi,
9. W. I. Weis,
10. R. O. Dror,
11. X. Chen,
12. R. J. Lefkowitz,
13. B. K. Kobilka
, Mechanism of intracellular allosteric β₂AR antagonist revealed by X-ray crystal structure. Nature 548, 480–484 (2017).
OpenUrl

View Abstract

[1] M. Sigal,
C. Y. Logan,
M. Kapalczynska,
H.-J. Mollenkopf,
H. Berger,
B. Wiedenmann,
R. Nusse,
M. R. Amieva,
T. F. Meyer
, Stromal R-spondin orchestrates gastric epithelial stem cells and gland homeostasis. Nature 548, 451–455 (2017).
OpenUrl

[2] M. Sigal,

[3] C. Y. Logan,

[4] M. Kapalczynska,

[5] H.-J. Mollenkopf,

[6] H. Berger,

[7] B. Wiedenmann,

[8] R. Nusse,

[9] M. R. Amieva,

[10] T. F. Meyer

[11] K. J. Mackenzie,
P. Carroll,
C.-A. Martin,
O. Murina,
A. Fluteau,
D. J. Simpson,
N. Olova,
H. Sutcliffe,
J. K. Rainger,
A. Leitch,
R. T. Osborn,
A. P. Wheeler,
M. Nowotny,
N. Gilbert,
T. Chandra,
M. A. M. Reijns,
A. P. Jackson
, cGAS surveillance of micronuclei links genome instability to innate immunity. Nature 548, 461–465 (2017).
OpenUrl

[12] K. J. Mackenzie,

[13] P. Carroll,

[14] C.-A. Martin,

[15] O. Murina,

[16] A. Fluteau,

[17] D. J. Simpson,

[18] N. Olova,

[19] H. Sutcliffe,

[20] J. K. Rainger,

[21] A. Leitch,

[22] R. T. Osborn,

[23] A. P. Wheeler,

[24] M. Nowotny,

[25] N. Gilbert,

[26] T. Chandra,

[27] M. A. M. Reijns,

[28] A. P. Jackson

[29] S. M. Harding,
J. L. Benci,
J. Irianto,
D. E. Discher,
A. J. Minn,
R. A. Greenberg
, Mitotic progression following DNA damage enables pattern recognition within micronuclei. Nature 548, 466–470 (2017).
OpenUrl

[30] S. M. Harding,

[31] J. L. Benci,

[32] J. Irianto,

[33] D. E. Discher,

[34] A. J. Minn,

[35] R. A. Greenberg

[36] S. Goel,
M. J. DeCristo,
A. C. Watt,
H. BrinJones,
J. Sceneay,
B. B. Li,
N. Khan,
J. M. Ubellacker,
S. Xie,
O. Metzger-Filho,
J. Hoog,
M. J. Ellis,
C. X. Ma,
S. Ramm,
I. E. Krop,
E. P. Winer,
T. M. Roberts,
H.-J. Kim,
S. S. McAllister,
J. J. Zhao
, CDK4/6 inhibition triggers anti-tumour immunity. Nature 548, 471–475 (2017).
OpenUrl

[37] S. Goel,

[38] M. J. DeCristo,

[39] A. C. Watt,

[40] H. BrinJones,

[41] J. Sceneay,

[42] B. B. Li,

[43] N. Khan,

[44] J. M. Ubellacker,

[45] S. Xie,

[46] O. Metzger-Filho,

[47] J. Hoog,

[48] M. J. Ellis,

[49] C. X. Ma,

[50] S. Ramm,

[51] I. E. Krop,

[52] E. P. Winer,

[53] T. M. Roberts,

[54] H.-J. Kim,

[55] S. S. McAllister,

[56] J. J. Zhao

[57] X. Liu,
S. Ahn,
A. W. Kahsai,
K.-C. Meng,
N. R. Latorraca,
B. Pani,
A. J. Venkatakrishnan,
A. Masoudi,
W. I. Weis,
R. O. Dror,
X. Chen,
R. J. Lefkowitz,
B. K. Kobilka
, Mechanism of intracellular allosteric β₂AR antagonist revealed by X-ray crystal structure. Nature 548, 480–484 (2017).
OpenUrl

[58] X. Liu,

[59] S. Ahn,

[60] A. W. Kahsai,

[61] K.-C. Meng,

[62] N. R. Latorraca,

[63] B. Pani,

[64] A. J. Venkatakrishnan,

[65] A. Masoudi,

[66] W. I. Weis,

[67] R. O. Dror,

[68] X. Chen,

[69] R. J. Lefkowitz,

[70] B. K. Kobilka

Papers of note in Nature 548 (7668)

Highlighted Articles

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