The N-terminus of the Chlamydia trachomatis effector Tarp engages the host Hippo pathway DOI Creative Commons
George F. Aranjuez, Om Prakash Patel,

Dev Patel

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 12, 2024

is an obligate, intracellular Gram-negative bacteria and the leading bacterial STI in United States.

Language: Английский

The Hippo kinases control inflammatory Hippo signaling and restrict bacterial infection in phagocytes DOI Creative Commons
Brendyn M. St. Louis, Sydney M. Quagliato, Yuting Su

et al.

mBio, Journal Year: 2024, Volume and Issue: 15(5)

Published: April 16, 2024

The Hippo kinases MST1 and MST2 initiate a highly conserved signaling cascade called the pathway that limits organ size tumor formation in animals. Intriguingly, pathogens hijack this host during infection, but role of MST1/2 innate immune cells against is unclear. In report, we generated

Language: Английский

Citations

4
Human papillomaviruses: Knowns, mysteries, and unchartered territories DOI

Maya K. Gelbard,

Karl Münger

Journal of Medical Virology, Journal Year: 2023, Volume and Issue: 95(10)

Published: Oct. 1, 2023

Abstract There has been an explosion in the number of papillomaviruses that have identified and fully sequenced. Yet only a minute fraction these studied any detail. Most our molecular research efforts focused on E6 E7 proteins “high‐risk,” cancer‐associated human (HPVs). Interactions high‐risk HPV with their respective cellular targets, p53 retinoblastoma tumor suppressors, investigated Some thus questioned if remains exciting worthwhile area investigation. However, fundamentally new insights biological activities targets discovered previously unstudied HPVs newly associated diseases. infections continue to be important cause morbidity mortality since there are no antivirals combat infections, should remain attractive investigators biomedical funding agencies, alike.

Language: Английский

Citations

8
The effects of HPV oncoproteins on host communication networks: Therapeutic connotations DOI
Josipa Skelin, Ho Yin Luk,

Dražan Butorac

et al.

Journal of Medical Virology, Journal Year: 2023, Volume and Issue: 95(12)

Published: Dec. 1, 2023

Abstract Human papillomavirus (HPV) infections are a leading cause of viral‐induced malignancies worldwide, with prominent association cervical and head neck cancers. The pivotal role HPV oncoproteins, E5, E6, E7, in manipulating cellular events, which contribute to viral pathogenesis various ways, has been extensively documented. This article reviews the influence oncoproteins on signaling pathways within host cell, shedding light underlying molecular mechanisms. A comprehensive understanding these alterations is essential for development targeted therapies strategies combat HPV‐induced premalignancies prevent their progress cancer. Furthermore, this review underscores intricate interplay between some most important pathways: Notch, Wnt/β‐catenin, MAPK, JAK/STAT, PI3K AKT/mTOR. treatment efficacies currently available inhibitors an HPV‐positive context also discussed. highlights importance continued research advance our knowledge enhance therapeutic interventions HPV‐associated diseases.

Language: Английский

Citations

6
HPV8-induced STAT3 activation led keratinocyte stem cell expansion in human actinic keratoses DOI Creative Commons
Huw Morgan, Carlotta Olivero, Boris Shorning

et al.

JCI Insight, Journal Year: 2024, Volume and Issue: 9(15)

Published: June 25, 2024

Despite epidermal turnover, the skin is host to a complex array of microbes including viruses, such as human papillomavirus (HPV), which must infect and manipulate keratinocyte stem cells (KSC) survive. This crosstalk between virome KSC populations remains largely unknown. Here, we investigated effect HPV8 on KSCs using various mouse models. We observed that early region gene E6 specifically caused Lrig1+ hair follicle junctional zone proliferation expansion, would facilitate viral transmission. Within specifically, bound intracellular p300 phosphorylate STAT3 transcriptional regulatory node. induces ΔNp63 expression, resulting in expansion into overlying epidermis. was associated with 70% actinic keratoses (AK). Together these results define "hit run" mechanism for keratosis an KSCs, lacks melanosome protection thus susceptible sun-light-induced malignant transformation.

Language: Английский

Citations

1
HPV18 E7 inhibits LATS1 kinase and activates YAP1 by degrading PTPN14 DOI Creative Commons
William J. Blakely, Joshua Hatterschide, Elizabeth White

et al.

mBio, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 9, 2024

ABSTRACT High-risk human papillomavirus (HPV) oncoproteins inactivate cellular tumor suppressors to reprogram host cell signaling pathways. HPV E7 proteins bind and degrade the suppressor PTPN14, thereby promoting nuclear localization of YAP1 oncoprotein inhibiting keratinocyte differentiation. is a transcriptional coactivator that drives epithelial stemness self-renewal. activity inhibited by highly conserved Hippo pathway, which frequently inactivated in cancers. MST1/2 LATS1/2 kinases form core kinase cascade. Active LATS1 phosphorylated on threonine 1079 inhibits phosphorylating it amino acids including serine 127. Here, we tested effect high-risk (carcinogenic) HPV18 pathway activity. We found either PTPN14 knockout or degradation decreased phosphorylation T1079 S127 keratinocytes Conversely, PTPN14-dependent differentiation required LATS certain PPxY motifs PTPN14. Neither nor putative phosphatase active sites were for promote Together, these data support inactivation reduce activity, IMPORTANCE The cascade YAP1, an driver There mounting evidence targeted viruses papillomavirus. promotes carcinogenic requires Blocking E7-dependent activation could inhibit HPV-mediated carcinogenesis, but mechanism activates has not been elucidated. Here report degrading kinase, reducing inhibitory YAP1. These can activate strengthen link between cells.

Language: Английский

Citations

1
HPV18 E7 inhibits LATS1 kinase and activates YAP1 by degrading PTPN14 DOI Creative Commons
William J. Blakely, Joshua Hatterschide, Elizabeth White

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 7, 2024

ABSTRACT High-risk human papillomavirus (HPV) oncoproteins inactivate cellular tumor suppressors to reprogram host cell signaling pathways. HPV E7 proteins bind and degrade the suppressor PTPN14, thereby promoting nuclear localization of YAP1 oncoprotein inhibiting keratinocyte differentiation. is a transcriptional coactivator that drives epithelial stemness self-renewal. activity inhibited by highly conserved Hippo pathway, which frequently inactivated in cancers. MST1/2 LATS1/2 kinases form core kinase cascade. Active LATS1 phosphorylated on threonine 1079 inhibits phosphorylating it amino acids including serine 127. Here, we tested effect high-risk (carcinogenic) HPV18 pathway activity. We found either PTPN14 knockout or degradation decreased phosphorylation T1079 S127 keratinocytes Conversely, PTPN14-dependent differentiation required LATS certain PPxY motifs PTPN14. Neither nor putative phosphatase active site were for promote Taken together, these data support inactivation reduce activity, SIGNIFICANCE The cascade YAP1, an driver There mounting evidence targeted viruses papillomavirus. promotes carcinogenic requires Blocking E7-dependent activation could inhibit HPV-mediated carcinogenesis, but mechanism activates has not been elucidated. Here report degrading kinase, reducing inhibitory YAP1. These can activate strengthen link between cells.

Language: Английский

Citations

0
The N-terminus of the Chlamydia trachomatis effector Tarp engages the host Hippo pathway DOI Creative Commons
George F. Aranjuez, Om Prakash Patel,

Dev Patel

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 12, 2024

is an obligate, intracellular Gram-negative bacteria and the leading bacterial STI in United States.

Language: Английский

Citations

0