Dataset Information

Cathepsin L Regulates Metabolic Networks Controlling Rapid Cell Growth and Proliferation

ABSTRACT: Rapidly proliferating cells reshape their metabolism to satisfy their ever-lasting need for building blocks. This phenomenon is exemplified in certain malignant conditions but also occurs during embryonic development, when cells rely heavily on glycolytic metabolism to exploit their metabolic intermediates for biosynthetic routes. How cells regulate this metabolic makeover is currently unknown. Here we report that loss of cathepsin L (CtsL) is associated with fast proliferation rate and enhanced glycolytic metabolism that depend on lactate dehydrogenase A (LDHA) activity. Furthermore, we show that CtsL inhibition led to increased LDHA expression, suggesting of a causal relationship between LDHA expression and function. In conclusion, we propose that CtsL regulate this metabolic circuit to keep cell division under check.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Embryo, Fibroblast

SUBMITTER: Farnusch Kaschani

LAB HEAD: Farnusch Kaschani

PROVIDER: PXD011588 | Pride | 2019-05-06

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 44

Publications

Cathepsin L Regulates Metabolic Networks Controlling Rapid Cell Growth and Proliferation.

Weiss-Sadan Tommy T Itzhak Gal G Kaschani Farnusch F Yu Zhanru Z Mahameed Mohamed M Anaki Adi A Ben-Nun Yael Y Merquiol Emmanuelle E Tirosh Boaz B Kessler Benedikt B Kaiser Markus M Blum Galia G

Molecular & cellular proteomics : MCP 20190422 7

Rapidly proliferating cells reshape their metabolism to satisfy their ever-lasting need for cellular building blocks. This phenomenon is exemplified in certain malignant conditions such as cancer but also during embryonic development when cells rely heavily on glycolytic metabolism to exploit its metabolic intermediates for biosynthetic processes. How cells reshape their metabolism is not fully understood. Here we report that loss of cathepsin L (Cts L) is associated with a fast proliferation ra ...[more]

PMID: 31010818

Similar Datasets

Project description:Hypoxia in stem cell niches and inner core of solid tumors contributes to cellular senescence and differentiation inhibition. It directly increases histone methylationby inhibiting the activities of O2-and α-ketoglutarate (α-KG)-dependent histone lysine demethylases. This study is the first to demonstrate how the hypoxic increment of methylated histones cross-talks with other epigenetic changes, such as histone clipping and heterochromatin redistribution, named senescence-associated heterochromatin foci (SAHF), which are found during oncogene-induced senescence (OIS). This study showed that Raf activation in primary human fibroblasts IMR90 increases mature cathepsin L (CTSL)-mediated cleavage of H3, H2B, and H4. Hypoxia prevented H3 cleavage not by inhibiting CTSL but by increasing H3K18me3 and H3K23me3 nearby cleaved site of H3. Forced expression of cleaved H3 in IMR90 cells induced senescence even under hypoxia, suggesting that hypoxia breaks this positive feedback senescence driving circle by increasing methylated histones. The decrease in methylated histones is necessary for OIS to trigger histone clipping and SAHFs, but hypoxia maintains methylated histones to prevent both. Forced reduction of methylated histones in hypoxic cells using inhibitors of methyl-transferases makes hypoxic conditions unable to prevent OIS from inducing both histone clipping and SAHFs. Reversely forced enhancement of methylated histones in normoxic cells using inhibitors of histone demethylases protected histones from clipping during OIS but failed to block SAHFs. Altogether, the maintenance of methylated histones, especially H3K23me3 and H3K18me3, is sufficient to protect histones from clipping during OIS, but not for inhibiting SAHFs, suggesting that besides inhibiting KDMs, hypoxia adopts other methods to inhibit SAHFs. These findings provide a novel mechanism by which hypoxia affects cell fate by increasing methylated histones that protect histones and chromatin from dramatic epigenetic changes.

			Action	DRS
	ACE0020_TWS18_01.raw	Raw
	ACE0020_TWS18_02.raw	Raw
	ACE0020_TWS18_03.raw	Raw
	ACE0020_TWS21_01.raw	Raw
	ACE0020_TWS21_02.raw	Raw