Sajjad, H. | bioRxiv Science

bioRxiv2026

OSTM1 is a ubiquitin E3 ligase that suppresses B-cell malignancy by activating the cAMP/PKA/CREB pathway

Osteoclastogenesis-associated transmembrane protein 1 (OSTM1) is a glycosylated, membrane-integral protein that regulates lysosomal homeostasis, with loss-of-function mutations causing autosomal recessive osteopetrosis. Through a whole-genome CRISPR/Cas9 screen, we identified OSTM1 as a previously unrecognized tumor suppressor in B-cell malignancies. Consistent with this role, OSTM1 is frequently deleted or downregulated across a broad spectrum of human B-cell cancers. In mice, B-cell-specific monoallelic or biallelic ablation of Ostm1 cooperates with Cdkn2a loss to drive lymphomagenesis with near-complete penetrance. Mechanistically, we uncover a cytosolic, non-glycosylated fraction of OSTM1 that functions as a ubiquitin E3 ligase to promote proteasomal degradation of phosphodiesterase 3B (PDE3B). As PDE3B hydrolyzes cAMP and suppresses the tumor-protective PKA/CREB/CREBBP signaling axis, loss of OSTM1 leads to PDE3B stabilization, attenuation of cAMP signaling, and enhanced oncogenic transformation. Together, our findings establish OSTM1 as a critical suppressor of B-cell lymphomagenesis through regulation of the cAMP/PKA/CREB pathway.

cancer biology↗

bioRxiv2020

Comprehensive studies of Head Maralla, Punjab, Pakistan vegetation for ethnopharmacological and ethnobotanical uses and their elaboration through quantitative indices

Head Maralla is a non-recognized wetland with diversified flora that becomes focus of current studies. Whole plant or their parts are being used for treating various maladies and they are the integral part of livelihood in the area. Unique species including Osmunda regalis is used for blood and renal diseases purifier. Wild plant resources are key to traditional ethnobotanical knowledge based practices and industrial applications. Current study reports Head Marala inhabitants interaction with these resources and identify priorities at species and habitat level for conservation. Four sites viz., River Tavi, Upstream Chenab, River Manawarwala Tavi and Bhalolpur were designated to record traditional knowledge through questionnaire and interviews during field trips. One hundred nineteen (119) plant species were identified belonging to 54 families, of which 87 species were of dicot, 12monocots, 05ferns, and 4 species of bryophytes. Fifty percent of the plant species were utilized as a whole for therapeutic purposes, followed by leaves which had more than 20% usage of total consumption. Ailments viz., urination (14%) followed by cough (8%), cold (7%), stomach (6%), asthma (6%), constipation (5%), laxative (5%), diarrhea (4%) etc., were associated with vegetation. Bronchial disorders, pneumonia, dyspepsia, anthelmintic and kidney stones, etc., were also among other diseases commonly cured by traditional knowledge. Fifteen percent of vegetation contributes as fodder species consumed by local community for livestock while almost 17% of local plants were utilized for industrial purposes like timber, fuel, furniture, wooden pots and sports goods. In conclusion the ecosystem of Head Maralla is a complex of aquatic, terrestrial and agricultural land that is located on climatic and geographical divides, which further add to botanical interest as included many wetland habitats with unique diversity of plants. It is suggested to devise comprehensive conservation strategies to safe indigenous knowledge in systematic way for comprehending ecological services.

plant biology↗