Hgs physically interacts with Smad5 and attenuates BMP signaling

Haag, Jill D.; Chubinskaya, Susan; Aigner, Thomas

doi:10.1016/j.yexcr.2006.01.019

Cited by 7 publications

(4 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(B) Transcript levels of the endosome-localized hGS, (c) Smurf1 and Smurf2 and (D) Man1 and Net25 exhibit distinct profiles corresponding to progressive changes in the cellular populations throughout the first wave of spermatogenesis. Man1 transcript levels are highest between days 18 and 21, concordant with the prevalence of spermatocytes while Hgs and Net25 levels peak around day [26][27][28][29][30][31][32][33][34][35] cells, compared to late pachytene spermatocytes (Fig. 4e).…”

Section: Resultsmentioning

confidence: 53%

“…34 Importantly, as activin opposes BMP4 actions at this age by downregulating c-kit synthesis, 9 it is essential to differentially regulate spermatogonial responses to activin and BMP. As HGS interacts with SMAD5 to repress BMP-induced transcription in human chondrocytes 35 and MAN1 abrogates SMAD1-and SMAD5-mediated BMP signaling, 36 the absence of Hgs transcripts and MAN1 protein in 5 dpp spermatogonia may reflect a signaling status in germ cells that is permissive to BMP actions as they begin to differentiate. a smad3-selective response of developing sertoli cells to activin corresponds to regulated expression of Zfyve9 and hgs.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

TGFβ superfamily signalling regulators are differentially expressed in the developing and adult mouse testis

et al. 2011

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

TGFβ superfamily signalling regulators are differentially expressed in the developing and adult mouse testis

et al. 2011

View full text Add to dashboard Cite

“…In the case of the ESCRT-0 component, it could serve as a positive and negative regulator of RTK signaling during Drosophila development [ 54 ]. Overdosed HGS was also reported to attenuate BMP-dependent transcriptional responses [ 55 ]. Similarly, some ESCRT members were found to play a role in the yeast transcriptional control [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

The Dual Role of an ESCRT-0 Component HGS in HBV Transcription and Naked Capsid Secretion

et al. 2015

View full text Add to dashboard Cite

The Endosomal Sorting Complex Required for Transport (ESCRT) is an important cellular machinery for the sorting and trafficking of ubiquitinated cargos. It is also known that ESCRT is required for the egress of a number of viruses. To investigate the relationship between ESCRT and hepatitis B virus (HBV), we conducted an siRNA screening of ESCRT components for their potential effect on HBV replication and virion release. We identified a number of ESCRT factors required for HBV replication, and focused our study here on HGS (HRS, hepatocyte growth factor-regulated tyrosine kinase substrate) in the ESCRT-0 complex. Aberrant levels of HGS suppressed HBV transcription, replication and virion secretion. Hydrodynamic delivery of HGS in a mouse model significantly suppressed viral replication in the liver and virion secretion in the serum. Surprisingly, overexpression of HGS stimulated the release of HBV naked capsids, irrespective of their viral RNA, DNA, or empty contents. Mutant core protein (HBc 1–147) containing no arginine-rich domain (ARD) failed to secrete empty virions with or without HGS. In contrast, empty naked capsids of HBc 1–147 could still be promoted for secretion by HGS. HGS exerted a strong positive effect on the secretion of naked capsids, at the expense of a reduced level of virions. The association between HGS and HBc appears to be ubiquitin-independent. Furthermore, HBc is preferentially co-localized with HGS near the cell periphery, instead of near the punctate endosomes in the cytoplasm. In summary, our work demonstrated the importance of an optimum level of HGS in HBV propagation. In addition to an effect on HBV transcription, HGS can diminish the pool size of intracellular nucleocapsids with ongoing genome maturation, probably in part by promoting the secretion of naked capsids. The secretion routes of HBV virions and naked capsids can be clearly distinguished based on the pleiotropic effect of HGS involved in the ESCRT-0 complex.

show abstract

“…For example, much less is known about HGS. HGS functions downstream of cytokine and growth factor signaling 31 and is involved in vesicular trafficking, autophagosome formation, 32 DNA synthesis inhibition, and bone morphogenic protein (BMP) signaling, 33 a pathway that is closely coregulated with TGF-␤ signaling. In fact, the 2 nonoverlapping hits from duplicate screens in THP-1, BMPR1A and ACVRL1 (Figure 3B), also belong to the BMP-and TGF-␤-signaling networks, indicating that all hits from replicate THP-1 siRNA screens either overlap directly or share similar molecular concepts.…”

Section: Discussionmentioning

confidence: 99%

RNAi screening of the kinome with cytarabine in leukemias

Tibes

Bogenberger

Chaudhuri

et al. 2012

Blood

View full text Add to dashboard Cite

To identify rational therapeutic combinations with cytarabine (Ara-C), we developed a high-throughput, small-interference RNA (siRNA) platform for myeloid leukemia cells. Of 572 kinases individually silenced in combination with Ara-C, silencing of 10 (1.7%) and 8 (1.4%) kinases strongly increased Ara-C activity in TF-1 and THP-1 cells, respectively. The strongest molecular concepts emerged around kinases involved in cell-cycle checkpoints and DNA-damage repair. In confirmatory siRNA assays, inhibition of WEE1 resulted in more potent and universal sensitization across myeloid cell lines than siRNA inhibition of PKMYT1, CHEK1, or ATR. Treatment of 8 acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML) cell lines with commercial and the first-in-class clinical WEE1 kinase inhibitor MK1775 confirmed sensitization to Ara-C up to 97-fold. Ex vivo, adding MK1775 substantially reduced viability in 13 of 14 AML, CML, and myelodysplastic syndrome patient samples compared with Ara-C alone. Maximum sensitization occurred at lower to moderate concentrations of both drugs. Induction of apoptosis was increased using a combination of Ara-C and MK1775 compared with using either drug alone. WEE1 is expressed in primary AML, ALL, and CML specimens. Data from this first siRNA-kinome sensitizer screen suggests that inhibiting WEE1 in combination with Ara-C is a rational combination for the treatment of myeloid and lymphoid leukemias.

show abstract

Hgs physically interacts with Smad5 and attenuates BMP signaling

Cited by 7 publications

References 46 publications

TGFβ superfamily signalling regulators are differentially expressed in the developing and adult mouse testis

TGFβ superfamily signalling regulators are differentially expressed in the developing and adult mouse testis

The Dual Role of an ESCRT-0 Component HGS in HBV Transcription and Naked Capsid Secretion

RNAi screening of the kinome with cytarabine in leukemias

Contact Info

Product

Resources

About