共 58 条
Genetic elimination of suppressor of fused reveals an essential repressor function in the mammalian Hedgehog signaling pathway
被引:404
作者:

Svärd, J
论文数: 0 引用数: 0
h-index: 0
机构: Karolinska Inst, Novum, Dept Biosci, SE-14157 Huddinge, Sweden

Henricson, KH
论文数: 0 引用数: 0
h-index: 0
机构: Karolinska Inst, Novum, Dept Biosci, SE-14157 Huddinge, Sweden

Persson-Lek, M
论文数: 0 引用数: 0
h-index: 0
机构: Karolinska Inst, Novum, Dept Biosci, SE-14157 Huddinge, Sweden

Rozell, B
论文数: 0 引用数: 0
h-index: 0
机构: Karolinska Inst, Novum, Dept Biosci, SE-14157 Huddinge, Sweden

Lauth, M
论文数: 0 引用数: 0
h-index: 0
机构: Karolinska Inst, Novum, Dept Biosci, SE-14157 Huddinge, Sweden

Bergstrm, Å
论文数: 0 引用数: 0
h-index: 0
机构: Karolinska Inst, Novum, Dept Biosci, SE-14157 Huddinge, Sweden

Ericson, J
论文数: 0 引用数: 0
h-index: 0
机构: Karolinska Inst, Novum, Dept Biosci, SE-14157 Huddinge, Sweden

Toftgård, R
论文数: 0 引用数: 0
h-index: 0
机构: Karolinska Inst, Novum, Dept Biosci, SE-14157 Huddinge, Sweden

Teglund, S
论文数: 0 引用数: 0
h-index: 0
机构: Karolinska Inst, Novum, Dept Biosci, SE-14157 Huddinge, Sweden
机构:
[1] Karolinska Inst, Novum, Dept Biosci, SE-14157 Huddinge, Sweden
[2] Karolinska Inst, Dept Cell & Mol Biol, SE-17177 Stockholm, Sweden
[3] Karolinska Univ Hosp, Karolinska Inst, Dept Lab Med, SE-14186 Huddinge, Sweden
关键词:
D O I:
10.1016/j.devcel.2005.12.013
中图分类号:
Q2 [细胞生物学];
学科分类号:
071009 ;
090102 ;
摘要:
The Hedgehog (Hh) pathway plays important roles during embryogenesis and carcinogenesis. Here, we show that ablation of the mouse Suppressor of fused (Sufu), an intracellular pathway component, leads to embryonic lethality at similar to E9.5 with cephalic and neural tube defects. Fibroblasts derived from Sufu(-/-) embryos showed high Gli-mediated Hh pathway activity that could not be modulated at the level of Smoothened and could only partially be blocked by PKA activation. Despite the robust constitutive pathway activation in the Sufu(-/-) fibroblasts, the GLI1 steady-state localization remained largely cytoplasmic, implying the presence of an effective nuclear export mechanism. Sufu(+/-) mice develop a skin phenotype with basaloid changes and jaw keratocysts, characteristic features of Gorlin syndrome, a human genetic disease linked to enhanced Hh signaling. Our data demonstrate that, in striking contrast to Drosophila, in mammals, Sufu has a central role, and its loss of function leads to potent ligand-independent activation of the Hh pathway.
引用
收藏
页码:187 / 197
页数:11
相关论文
共 58 条
[11]
Characterization of the physical interaction of Gli proteins with SUFU proteins
[J].
Dunaeva, M
;
Michelson, P
;
Kogerman, P
;
Toftgard, R
.
JOURNAL OF BIOLOGICAL CHEMISTRY,
2003, 278 (07)
:5116-5122

Dunaeva, M
论文数: 0 引用数: 0
h-index: 0
机构: Karolinska Inst, NOVUM, Ctr Nutr & Toxicol, Dept Biosci, SE-14157 Huddinge, Sweden

Michelson, P
论文数: 0 引用数: 0
h-index: 0
机构: Karolinska Inst, NOVUM, Ctr Nutr & Toxicol, Dept Biosci, SE-14157 Huddinge, Sweden

Kogerman, P
论文数: 0 引用数: 0
h-index: 0
机构: Karolinska Inst, NOVUM, Ctr Nutr & Toxicol, Dept Biosci, SE-14157 Huddinge, Sweden

Toftgard, R
论文数: 0 引用数: 0
h-index: 0
机构:
Karolinska Inst, NOVUM, Ctr Nutr & Toxicol, Dept Biosci, SE-14157 Huddinge, Sweden Karolinska Inst, NOVUM, Ctr Nutr & Toxicol, Dept Biosci, SE-14157 Huddinge, Sweden
[12]
Altered neural cell fates and medulloblastoma in mouse patched mutants
[J].
Goodrich, LV
;
Milenkovic, L
;
Higgins, KM
;
Scott, MP
.
SCIENCE,
1997, 277 (5329)
:1109-1113

Goodrich, LV
论文数: 0 引用数: 0
h-index: 0
机构: STANFORD UNIV, SCH MED, DEPT DEV BIOL, STANFORD, CA 94305 USA

Milenkovic, L
论文数: 0 引用数: 0
h-index: 0
机构: STANFORD UNIV, SCH MED, DEPT DEV BIOL, STANFORD, CA 94305 USA

Higgins, KM
论文数: 0 引用数: 0
h-index: 0
机构: STANFORD UNIV, SCH MED, DEPT DEV BIOL, STANFORD, CA 94305 USA

Scott, MP
论文数: 0 引用数: 0
h-index: 0
机构: STANFORD UNIV, SCH MED, DEPT DEV BIOL, STANFORD, CA 94305 USA
[13]
Nevoid basal cell carcinoma (Gorlin) syndrome
[J].
Gorlin, RJ
.
GENETICS IN MEDICINE,
2004, 6 (06)
:530-539

Gorlin, RJ
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Minnesota, Sch Dent, Minneapolis, MN 55455 USA Univ Minnesota, Sch Dent, Minneapolis, MN 55455 USA
[14]
The magnitude of hedgehog signaling activity defines skin tumor phenotype
[J].
Grachtchouk, V
;
Grachtchouk, M
;
Lowe, L
;
Johnson, T
;
Wei, LB
;
Wang, AQ
;
de Sauvage, F
;
Dlugosz, AA
.
EMBO JOURNAL,
2003, 22 (11)
:2741-2751

Grachtchouk, V
论文数: 0 引用数: 0
h-index: 0
机构: Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA

Grachtchouk, M
论文数: 0 引用数: 0
h-index: 0
机构: Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA

Lowe, L
论文数: 0 引用数: 0
h-index: 0
机构: Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA

Johnson, T
论文数: 0 引用数: 0
h-index: 0
机构: Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA

Wei, LB
论文数: 0 引用数: 0
h-index: 0
机构: Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA

Wang, AQ
论文数: 0 引用数: 0
h-index: 0
机构: Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA

de Sauvage, F
论文数: 0 引用数: 0
h-index: 0
机构: Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA

Dlugosz, AA
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA
[15]
Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome
[J].
Hahn, H
;
Wicking, C
;
Zaphiropoulos, PG
;
Gailani, MR
;
Shanley, S
;
Chidambaram, A
;
Vorechovsky, I
;
Holmberg, E
;
Unden, AB
;
Gillies, S
;
Negus, K
;
Smyth, I
;
Pressman, C
;
Leffell, DJ
;
Gerrard, B
;
Goldstein, AM
;
Dean, M
;
Toftgard, R
;
ChenevixTrench, G
;
Wainwright, B
;
Bale, AE
.
CELL,
1996, 85 (06)
:841-851

Hahn, H
论文数: 0 引用数: 0
h-index: 0
机构: NCI,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702

Wicking, C
论文数: 0 引用数: 0
h-index: 0
机构: NCI,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702

Zaphiropoulos, PG
论文数: 0 引用数: 0
h-index: 0
机构: NCI,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702

Gailani, MR
论文数: 0 引用数: 0
h-index: 0
机构: NCI,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702

Shanley, S
论文数: 0 引用数: 0
h-index: 0
机构: NCI,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702

Chidambaram, A
论文数: 0 引用数: 0
h-index: 0
机构: NCI,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702

Vorechovsky, I
论文数: 0 引用数: 0
h-index: 0
机构: NCI,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702

Holmberg, E
论文数: 0 引用数: 0
h-index: 0
机构: NCI,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702

Unden, AB
论文数: 0 引用数: 0
h-index: 0
机构: NCI,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702

Gillies, S
论文数: 0 引用数: 0
h-index: 0
机构: NCI,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702

Negus, K
论文数: 0 引用数: 0
h-index: 0
机构: NCI,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702

Smyth, I
论文数: 0 引用数: 0
h-index: 0
机构: NCI,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702

Pressman, C
论文数: 0 引用数: 0
h-index: 0
机构: NCI,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702

Leffell, DJ
论文数: 0 引用数: 0
h-index: 0
机构: NCI,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702

Gerrard, B
论文数: 0 引用数: 0
h-index: 0
机构: NCI,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702

Goldstein, AM
论文数: 0 引用数: 0
h-index: 0
机构: NCI,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702

Dean, M
论文数: 0 引用数: 0
h-index: 0
机构: NCI,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702

Toftgard, R
论文数: 0 引用数: 0
h-index: 0
机构: NCI,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702

ChenevixTrench, G
论文数: 0 引用数: 0
h-index: 0
机构: NCI,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702

Wainwright, B
论文数: 0 引用数: 0
h-index: 0
机构: NCI,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702

Bale, AE
论文数: 0 引用数: 0
h-index: 0
机构: NCI,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702
[16]
Intraflagellar transport is required in Drosophila to differentiate sensory cilia but not sperm
[J].
Han, YG
;
Kwok, BH
;
Kernan, MJ
.
CURRENT BIOLOGY,
2003, 13 (19)
:1679-1686

Han, YG
论文数: 0 引用数: 0
h-index: 0
机构: SUNY Stony Brook, Grad Program Genet, Stony Brook, NY 11794 USA

Kwok, BH
论文数: 0 引用数: 0
h-index: 0
机构: SUNY Stony Brook, Grad Program Genet, Stony Brook, NY 11794 USA

Kernan, MJ
论文数: 0 引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Grad Program Genet, Stony Brook, NY 11794 USA SUNY Stony Brook, Grad Program Genet, Stony Brook, NY 11794 USA
[17]
EXPRESSION OF A DELTA-HOMOLOG IN PROSPECTIVE NEURONS IN THE CHICK
[J].
HENRIQUE, D
;
ADAM, J
;
MYAT, A
;
CHITNIS, A
;
LEWIS, J
;
ISHHOROWICZ, D
.
NATURE,
1995, 375 (6534)
:787-790

HENRIQUE, D
论文数: 0 引用数: 0
h-index: 0
机构: UNIV OXFORD,DEPT ZOOL,IMPERIAL CANC RES FUND,ORGANOGENESIS LAB,BIOL UNIT,OXFORD OX1 3PS,ENGLAND

ADAM, J
论文数: 0 引用数: 0
h-index: 0
机构: UNIV OXFORD,DEPT ZOOL,IMPERIAL CANC RES FUND,ORGANOGENESIS LAB,BIOL UNIT,OXFORD OX1 3PS,ENGLAND

MYAT, A
论文数: 0 引用数: 0
h-index: 0
机构: UNIV OXFORD,DEPT ZOOL,IMPERIAL CANC RES FUND,ORGANOGENESIS LAB,BIOL UNIT,OXFORD OX1 3PS,ENGLAND

CHITNIS, A
论文数: 0 引用数: 0
h-index: 0
机构: UNIV OXFORD,DEPT ZOOL,IMPERIAL CANC RES FUND,ORGANOGENESIS LAB,BIOL UNIT,OXFORD OX1 3PS,ENGLAND

LEWIS, J
论文数: 0 引用数: 0
h-index: 0
机构: UNIV OXFORD,DEPT ZOOL,IMPERIAL CANC RES FUND,ORGANOGENESIS LAB,BIOL UNIT,OXFORD OX1 3PS,ENGLAND

ISHHOROWICZ, D
论文数: 0 引用数: 0
h-index: 0
机构: UNIV OXFORD,DEPT ZOOL,IMPERIAL CANC RES FUND,ORGANOGENESIS LAB,BIOL UNIT,OXFORD OX1 3PS,ENGLAND
[18]
Communicating with Hedgehogs
[J].
Hooper, JE
;
Scott, MP
.
NATURE REVIEWS MOLECULAR CELL BIOLOGY,
2005, 6 (04)
:306-317

Hooper, JE
论文数: 0 引用数: 0
h-index: 0
机构: Univ Colorado, Sch Med, Dept Cell & Dev Biol, Aurora, CO 80045 USA

Scott, MP
论文数: 0 引用数: 0
h-index: 0
机构: Univ Colorado, Sch Med, Dept Cell & Dev Biol, Aurora, CO 80045 USA
[19]
Hedgehog signalling in the mouse requires intraflagellar transport proteins
[J].
Huangfu, DW
;
Liu, AM
;
Rakeman, AS
;
Murcia, NS
;
Niswander, L
;
Anderson, KV
.
NATURE,
2003, 426 (6962)
:83-87

Huangfu, DW
论文数: 0 引用数: 0
h-index: 0
机构: Sloan Kettering Inst, Dev Biol Program, New York, NY 10021 USA

Liu, AM
论文数: 0 引用数: 0
h-index: 0
机构: Sloan Kettering Inst, Dev Biol Program, New York, NY 10021 USA

Rakeman, AS
论文数: 0 引用数: 0
h-index: 0
机构: Sloan Kettering Inst, Dev Biol Program, New York, NY 10021 USA

Murcia, NS
论文数: 0 引用数: 0
h-index: 0
机构: Sloan Kettering Inst, Dev Biol Program, New York, NY 10021 USA

Niswander, L
论文数: 0 引用数: 0
h-index: 0
机构: Sloan Kettering Inst, Dev Biol Program, New York, NY 10021 USA

Anderson, KV
论文数: 0 引用数: 0
h-index: 0
机构: Sloan Kettering Inst, Dev Biol Program, New York, NY 10021 USA
[20]
Sustained Hedgehog signaling is required for basal cell carcinoma proliferation and survival: conditional skin tumorigenesis recapitulates the hair growth cycle
[J].
Hutchin, ME
;
Kariapper, MST
;
Grachtchouk, M
;
Wang, AQ
;
Wei, LB
;
Cummings, D
;
Liu, JH
;
Michael, LE
;
Glick, A
;
Dlugosz, AA
.
GENES & DEVELOPMENT,
2005, 19 (02)
:214-223

Hutchin, ME
论文数: 0 引用数: 0
h-index: 0
机构: Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA

Kariapper, MST
论文数: 0 引用数: 0
h-index: 0
机构: Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA

论文数: 引用数:
h-index:
机构:

Wang, AQ
论文数: 0 引用数: 0
h-index: 0
机构: Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA

Wei, LB
论文数: 0 引用数: 0
h-index: 0
机构: Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA

Cummings, D
论文数: 0 引用数: 0
h-index: 0
机构: Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA

Liu, JH
论文数: 0 引用数: 0
h-index: 0
机构: Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA

Michael, LE
论文数: 0 引用数: 0
h-index: 0
机构: Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA

Glick, A
论文数: 0 引用数: 0
h-index: 0
机构: Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA

Dlugosz, AA
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA